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Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P <.001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment. [ABSTRACT FROM AUTHOR]

Methyltransferase-like protein 7A (METTL7A) is an m6A RNA methyltransferase that has been linked to cancer prognosis and drug resistance. However, a comprehensive analysis of METTL7A is lacking. The expression of METTL7A, prognostic performance, correlation with microsatellite instability (MSI), tumor mutational burden (TMB), and immune infiltration was investigated in The Cancer Genome Atlas (TCGA). Immunohistochemistry staining was applied to detect METTL7A in 6 tumors. METTL7A was significantly decreased in 19 cancers in TCGA including LUAD. Alterations of METTL7A include amplification and mutation, and epigenetic alterations revealed increased promoter methylation may result in down-regulation of METTL7A in LUAD. We also found that METTL7A was linked to both TMB and MSI in LUAD. METTL7A was increasingly correlated with invasive immune cells, while being negatively associated with Macrophages M0, Mast cells activated, activated memory CD4 T cells, CD8 T cells, and follicular helper T cells in several tumors. Additionally, METTL7A showed similar correlation with immune therapy-related genes across cancers. Our biological validation found that the protein levels of METTL7A were down-regulated in breast cancer (BRCA), endometrioid cancer (UCEC), colon cancer (COAD), prostate cancer (PRAD), and kidney clear cell carcinoma (KIRC), as detected by immunohistochemistry staining. Overall, our work indicates that METTL7A may serve as promising diagnostic and prognostic indicator of LUAD, and our work sheds light on the potential immunological and prognostic roles of METTL7A in human cancers. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the significance of chemotherapy (CT) among metaplastic breast cancer (MpBC), and to compare the survival outcomes between triple negative MpBC (MpBC-TNBC) and triple negative invasive ductal carcinoma (IDC-TNBC). SEER database was indexed to identify female unilateral primary MpBC diagnosed from 2010 to 2017. Patients were classified into neoadjuvant chemotherapy (NAC) with response (NAC-response), NAC-no response, adjuvant chemotherapy, and no CT. Breast cancer-specific survival (BCSS) and overall survival (OS) was estimated using the Kaplan–Meier method and compared by log-rank test. Cox regression was used to evaluate the independent prognostic factors. A 1:4 propensity score matching method was adopted to balance baseline differences. Altogether 1186 MpBC patients were enrolled, among them 181 received NAC, 647 received adjuvant CT and 358 did not receive any CT. Chemotherapy was an independent favorable prognostic factor. NAC-response and adjuvant CT had a significant or an obvious trend of survival improvement compared with NAC-no response or no CT. MpBC-TNBC was an independent unfavorable prognostic factor compared with IDC-TNBC. Among them, there was significant or trend of survival improvement among all TNBCs receiving NAC or adjuvant CT compared with no CT. Chemotherapy was of important significance to MpBC prognosis and should be integrated in comprehensive treatment for MpBC. [ABSTRACT FROM AUTHOR]

Heart failure (HF) and permanent atrial fibrillation (AF) interact mutually, exacerbating hemodynamic effects and causing adverse outcomes and increased healthcare costs. Monitoring hemodynamic indicators in patients with these comorbidities is crucial for effective clinical management. Transthoracic impedance cardiography (ICG) has been widely employed in assessing hemodynamic status in clinical settings. Given the limited research on the prognostic significance of ICG parameters in HF with permanent AF, we undertook this study. A total of 66 HF patients with permanent AF were included in this retrospective study, and the primary outcome was rehospitalization due to worsening HF within 180-day post-discharge. Cox regression analysis was performed to explore the connection between ICG-evaluated parameters and the outcome risk. Receiver operating characteristic (ROC) curve analysis determined the optimal cutoff values of risk factors, subsequently applied in plotting Kaplan Meier (KM) survival curves. Multivariate Cox regression analysis revealed that systemic vascular resistance (SVR) both on admission and at discharge independently predicted rehospitalization for worsening HF. ROC analysis established optimal SVR cutoff values: 320.89 (kPa s/L) on admission and 169.94 (kPa s/L) at discharge (sensitivity 70%, specificity 94.4%, area under the curve (AUC) 0.831, respectively, sensitivity 90%, specificity 55.6%, AUC 0.742). KM survival curves analysis showed that patients with SVR > 320.89 (kPa s/L) on admission had an 8.14-fold (P < 0.001) increased risk of the end-point event compared with those with SVR ≤ 320.89 (kPa s/L). Similarly, patients with SVR > 169.94 (kPa s/L) at discharge faced a risk elevated by 6.57 times (P = 0.002) relative to those with SVR ≤ 169.94 (kPa s/L). In HF patients with permanent AF, SVR measured by ICG emerges as an independent risk factor and clinical predictor for HF deterioration-related readmission within 180 days after discharge. Higher SVR levels, both upon admission and at discharge, correlate with an incremental rehospitalization risk. [ABSTRACT FROM AUTHOR]

Objectives: Despite the increasingly modern surgical techniques in the oncology field, the factors that influence postoperative prognosis in patients with hypopharyngeal and laryngeal carcinoma (HLC) remain unclear. The study aimed to evaluate the factors influencing the prognosis of HLC patients with pathological diagnosis of squamous cell carcinoma, and the findings are intended to direct follow-up management strategies. Methods: A retrospective cohort study was performed. The study population included 407 postoperative patients with HLC from 2011 to 2015. Univariate and multivariate analyses were used to examine the prognostic factors identified. Results: Based on univariate analysis results, smoking and alcohol history, tumor differentiation, preoperative radiotherapy, primary tumor sites, flap reconstruction, lymph node invasion (LNI), and preoperative albumin levels (PAL) significantly affects the prognosis of HLC patients (P <.05). Meanwhile, multivariate analysis revealed that smoking pack-year (OR = 1.002, 95% CI = 1.001 ∼ 1.003), primary tumor sites (OR = 6.241, 95% CI = 1.715 ∼ 18.433), LNI (OR = 2.869, 95% CI = 1.095 ∼ 8.743), and PAL (OR =.020, 95% CI =.004 ∼ 0.104) were associated with complications. Tumor differentiation (OR = 0.650, 95% CI =.383 ∼ 0.855), primary tumor sites (OR = 12.392, 95% CI = 3.290 ∼ 26.679), LNI (OR = 16.323, 95% CI = 2.726 ∼ 47.729), preoperative radiotherapy (OR = 9.300, 95% CI = 3.182 ∼ 27.181), and PAL (OR =.321, 95% CI =.141 ∼.732) were associated with overall survival rates. Conclusion: Smoking and alcohol history, tumor differentiation, LNI, primary tumor sites, flap reconstruction, PAL, and preoperative radiotherapy are crucial factors that influence the postoperative prognosis of patients with HLC. In addition, a monogram of five factors was established to predict the survival rates of HLC patients. [ABSTRACT FROM AUTHOR]

Methyltransferase-like 3 (METTL3) is the key subunit of methyltransferase complex responsible for catalyzing N6-methyladenosine (m6A) modification on mRNA, which is the most prevalent post-transcriptional modification in eukaryotes. In this study, we utilized online databases to analyze the association between METTL3 expression and various aspects of tumorigenesis, including gene methylation, immunity, and prognosis. Our investigation revealed that METTL3 serves as a prognostic marker and therapeutic target for liver hepatocellular carcinoma (LIHC). Through experimental studies, we observed frequent upregulation of METTL3 in LIHC tumor tissue and cells. Subsequent inhibition of METTL3 using a novel small molecule inhibitor, STM2457, significantly impeded tumor growth in LIHC cell lines, spheroids, and xenograft tumor model. Further, transcriptome and m6A sequencing of xenograft bodies unveiled that inhibition of METTL3-m6A altered genes enriched in SMAD and MAPK signaling pathways that are critical for tumorigenesis. These findings suggest that targeting METTL3 represents a promising therapeutic strategy for LIHC. [ABSTRACT FROM AUTHOR]

Background: Despite progress in the diagnosis and treatment of proliferative lupus nephritis (PLN), the prognosis remains unfavorable. Previous investigations have suggested that the deficiency of regulatory T cells (Tregs) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). But the prognostic value of Tregs in PLN remains controversial. This study aimed to investigate the association of Tregs with renal outcomes in patients with PLN. Methods: The baseline and follow-up data of patients with biopsy-proven PLN were collected in this study. All patients were divided into two groups according to whether the renal endpoint event occurred. Clinicopathologic features and therapeutic responses were compared between the two groups. Cox regression analyses curve fitting and threshold effect analysis were implemented to investigate the relationship between Tregs level and the long-term renal outcomes. The renal endpoint was defined as end-stage kidney disease (ESKD) or doubling the SCr value. Results: A total of 405 PLN patients were included. After a follow-up of 71.53 (53.13–97.47) months, 42 (10.4%) patients reached the renal endpoint. The Treg cell counts (16/μL) in the renal endpoint group were significantly decreased than that in the non-renal endpoint group (p < 0.001). Univariate and multivariate Cox regression analyses showed that the high level of Tregs was an independent protective factor for the long-term renal prognosis of PLN. Smooth curve fitting of the generalized additive mixed model analysis indicated that the risk of renal endpoint first decreased with Tregs and then slightly increased along with Treg cell levels. The segmented linear model revealed that when Treg cell counts <46/μL, the risk of renal endpoint decreased by 6.8% for every 1 μL increase in Treg levels (p = 0.0029). Conclusion: Treg cell counts are closely related to the long-term renal outcomes of patients with PLN, and increasing Treg cell levels may play an important role in improving the prognosis of the kidney, but there may be a turning point (i.e., threshold effect) at the Treg cell counts that leads to directional changes in the renal outcomes. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AE) is an immune-mediated encephalitis; nevertheless, its diagnosis in children remains challenging. This study aimed to reveal the clinical characteristics, diagnostic processes, and therapeutic outcomes of AE in children. A total of 18 children with AE were enrolled. Antibody assay was performed in the cerebrospinal fluid (CSF) and serum samples by indirect immunofluorescence. Electroencephalography (EEG) and magnetic resonance imaging (MRI) were monitored to reflect abnormal neural signals. In addition, demographics data, neurological symptoms, therapeutic strategies, and outcomes were recorded and analyzed. Convulsion (50.00%) and emotional disturbance (44.44%) were common clinical symptoms of AE. The biochemical parameters in the CSF had a relatively low diagnostic value. Antibodies in the CSF were dominant in the diagnosis of AE but those in the serum were limited in the diagnosis of anti-MOG or anti-LGI1 AE. In addition, all children showed abnormalities in EEG (72.22%) or MRI (66.67%). Methylprednisolone combined with sequential oral prednisone (83.33%) and gamma globulin (88.89%) were the dominant drugs, achieving an overall recovery rate of 72.22%. However, there were still two patients who had poor outcomes, including Patient 3 with a young age (two years old) and progressive symptom and Patient 12 with a long disease course before treatment (>120 days). The clinical manifestations of AE are varied in children. Antibody in the CSF was dominant, and EEG and MRI were instructive in the diagnosis of AE. Young age, progressive symptom, and prolonged disease course before treatment may contribute to poor outcomes. [ABSTRACT FROM AUTHOR]

Background: Gastric cardia adenocarcinoma (GCA) is a highly fatal form of cancer in humans. The aim of this study was to extract clinicopathological data of postoperative patients with GCA from the Surveillance, Epidemiology, and End Results database, analyze prognostic risk factors, and build a nomogram. Methods: In this study, the clinical information of 1448 patients with GCA who underwent radical surgery and were diagnosed between 2010 and 2015 was extracted from the SEER database. The patients were then randomly divided into training (n = 1013) and internal validation (n = 435) cohorts at a 7:3 ratio. The study also included an external validation cohort (n = 218) from a Chinese hospital. The study used the Cox and LASSO models to pinpoint the independent risk factors linked to GCA. The prognostic model was constructed according to the results of the multivariate regression analysis. To assess the predictive accuracy of the nomogram, four methods were used: C‐index, calibration curve, time‐dependent ROC curve, and DCA curve. Kaplan–Meier survival curves were also generated to illustrate the differences in cancer‐specific survival (CSS) between the groups. Results: The results of the multivariate Cox regression analysis showed that age, grade, race, marital status, T stage, and log odds of positive lymph nodes (LODDS) were independently associated with cancer‐specific survival in the training cohort. Both the C‐index and AUC values depicted in the nomogram were greater than 0.71. The calibration curve revealed that the nomogram's CSS prediction was consistent with the actual outcomes. The decision curve analysis suggested moderately positive net benefits. Based on the nomogram risk score, significant differences in survival between the high‐ and low‐risk groups were observed. Conclusions: Race, age, marital status, differentiation grade, T stage, and LODDS are independent predictors of CSS in patients with GCA after radical surgery. Our predictive nomogram constructed based on these variables demonstrated good predictive ability. The nomogram for postoperative patients with GCA we constructed has good predictive power and can help clinicians accurately assess patient prognosis and identify high‐risk patients to develop more personalized treatment plans. [ABSTRACT FROM AUTHOR]

The majority of patients are diagnosed when ovarian cancer (OC) has metastasized, making surgery and chemotherapy less effective. Thus, there is an urgent need to elucidate the mechanisms underlying metastasis and to further explore novel diagnostic biomarkers of OC metastasis. Here, we conducted a genome-wide CRISPR-Cas9 screen for anoikis resistance to identify key genes associated with OC metastasis. Further, bioinformatic analysis was performed using TCGA and GTEx datasets to explore the genes associated with OC progression and prognosis. After integrated analysis, the V-set and transmembrane domain-containing protein 2-like (VSTM2L) was identified as a crucial gene closely associated with OC metastasis, progression, and prognosis. Further validation using a patient-based cohort suggested that VSTM2L expression was significantly higher in metastatic lesions than in primary lesions. Subsequently, an in vitro assay showed that VSTM2L silencing increased SKOV3 cell death and hampered spheroid formation. Mechanistically, GSEA highlighted that epithelial-mesenchymal transition (EMT)-related pathways was positively associated with VSTM2L expression. Consistently, the validation based on the VSTM2L silence suggested the involvement of VSTM2L in EMT-related TGF-β and NF-κB signaling. Meanwhile, the addition of VSTM2L-containing medium did not provoke those signaling, indicating VSTM2L functions as an intracellular protein to activate TGF-β and NF-κB signaling. In summary, our study revealed that VSTM2L is a novel player involved in anoikis resistance and is a promising biomarker of OC metastasis and prognosis. • Genome-wide screening combined with bioinformatics identified VSTM2L as a promising biomarker for ovarian cancer. • VSTM2L regulates TGF-β and NF-κB signaling and promotes anoikis resistance. • VSTM2L functions as an intracellular protein to regulate EMT-related signaling. [ABSTRACT FROM AUTHOR]

• The sequence type 5 (ST5) lineage caused a significant burden on HIV-negative hosts in East Asia. • The high ST5 lineage infection rate was not due to environmental abundance. • Seven factors predicted acute death in patients without HIV who were infected with ST5 lineage. • We provided an understanding of the ST5 lineage associated with cryptococcosis. Cryptococcus neoformans sequence type 5 (ST5) lineage could infect immunocompetent hosts and cause a significant medical burden. We sought to identify characteristics and prognostic risk factors of ST5 lineage-associated cryptococcosis. Multilocus sequence typing and antifungal susceptibility testing were conducted for Cryptococcus isolates. The clinical and laboratory characteristics of cryptococcosis patients were investigated. The multivariable logistic regression identified variables independently associated with 30-day mortality in patients with ST5 lineage-associated cryptococcosis without HIV. The infection rate of the ST5 isolates was 89.4% (370/414) in China. The proportion of ST5 isolates with nonwild-type minimum inhibitory concentrations to amphotericin B, 5-flucytosine, voriconazole, posaconazole, itraconazole, and fluconazole were 0%, 5.4%, 0.3%, 1.4%, 0.3%, and 8.1%, respectively. The ST5 lineage-infected group exhibited significantly higher blood platelet count, lower blood cryptococcal antigen (CrAg) titer, lower cerebrospinal fluid (CSF) CrAg titer than the non-ST5 lineage-infected group, and lower hemoglobin and lower CSF CrAg titer than the Cryptococcus gattii isolates-infected group. Seven baseline parameters, including underlying disease, dyskinesia, anemia, high peripheral blood neutrophils, low platelet count, high CSF fungal burden, and high CSF opening pressure, were associated independently with the 30-day mortality of patients with ST5 lineage-associated cryptococcosis without HIV. Our study has provided an understanding of the ST5 lineage associated with cryptococcosis. [ABSTRACT FROM AUTHOR]

Introduction: Myometrial invasion is a prognostic factor for lymph node metastases and decreased survival in non-endometrioid endometrial carcinoma patients. Herein, we explored the mode of myometrial invasion diagnosis in FIGO stage I non-endometrioid carcinoma and evaluated the differences in diagnostic efficiency among intraoperative frozen section (IFS), intraoperative gross examination (IGE), magnetic resonance imaging (MRI), and computed tomography (CT) in clinical practice. Finally, we suggested which test should be routinely performed. Method: This was a historical cohort study nationwide with 30 centers in China between January 2000 and December 2019. Clinical data, including age, histology, method of myometrial invasion evaluation (MRI, CT, IGE, and IFS), and final diagnosis of postoperative paraffin sections, were collected from 490 non-endometrioid endometrial carcinoma (serous, clear cell, undifferentiated, mixed carcinoma, and carcinosarcoma) women in FIGO stage I. Results: Among the 490 patients, 89.59% presented myometrial invasion. The methods reported for myometrial invasion assessment were IFS in 23.47%, IGE in 69.59%, MRI in 37.96%, and CT in 10.20% of cases. The highest concordance was detected between IFS and postoperative paraffin sections (Kappa = 0.631, accuracy = 93.04%), followed by IGE (Kappa = 0.303, accuracy = 82.40%), MRI (Kappa = 0.131, accuracy = 69.35%), and CT (Kappa = 0.118, accuracy = 50.00%). A stable diagnostic agreement between IFS and the final results was also found through the years (2000–2012: Kappa = 0.776; 2013–2014: Kappa = 0.625; 2015–2016: Kappa = 0.545; 2017–2019: Kappa = 0.652). Conclusion: In China, the assessment of myometrial invasion in non-endometrioid endometrial carcinoma is often performed via IGE, but the reliability is relatively low in contrast to IFS. In clinical practice, IFS is a reliable method that can help accurately assess myometrial invasion and intraoperative decision-making (lymph node dissection or not). Hence, it should be routinely performed in non-endometrioid endometrial carcinoma patients. [ABSTRACT FROM AUTHOR]

Background: Early death remains a major factor in survival in APL. We aimed to analyze the risk factors for differentiation syndrome and early death in acute promyelocytic leukemia (APL). Methods: The clinical data of APL patients who were newly diagnosed at Mianyang Central Hospital from January 2013 to January 2022 were retrospectively analyzed. Results: Eighty-six newly diagnosed APL patients (37 males and 49 females) were included in this study. The median age was 46 (17–75) years. Sixty-one patients (70.9%) had low/intermediate-risk APL, and 25 patients (29.1%) had high-risk APL. The incidence of differentiation syndrome (DS) was 62.4%. The multivariate analysis showed that a peak white blood cell (WBC) count ≥16 × 10^9/L was an independent risk factor (OR = 11.000, 95% CI: 2.830–42.756, P = 0.001) for DS in all APL patients, while a WBC count ≥10 × 10^9/L on Day 5 was an independent risk factor for DS in low-intermediate risk APL patients (OR = 9.114, 95% CI: 2.384–34.849, P = 0.001). There were 31 patients (36.5%) with mild DS and 22 patients (25.9%) with severe DS. The multivariate analysis showed that WBC count ≥23 × 10^9/L at chemotherapy was an independent risk factor for severe DS (OR = 10.500, 95% CI: 2.344–47.034, P = 0.002). The rate of early death (ED) was 24.4% (21/86). The multivariate analysis showed that male gender (OR = 7.578,95% CI:1.136–50.551, P = 0.036), HGB < 65 g/L (OR = 16.271,95% CI:2.012–131.594, P = 0.009) and WBC count ≥7 × 10^9/L on Day 3(OR = 23.359,95% CI:1.825–298.959, P = 0.015) were independent risk factors for ED. The WBC count at diagnosis, WBC count on Day 3 and WBC count on Day 5 had moderate positive correlations with tumor necrosis factor-α (TNF-α) at diagnosis, and the correlation coefficients were 0.648 (P = 0.012), 0.615 (P = 0.033), and 0.609 (P = 0.035), respectively. The WBC count had no correlation with IL-6. Conclusion: During induction treatment, cytotoxic chemotherapy may need to be initiated to reduce the risk of DS for APL patients with a low-intermediate risk WBC count ≥10 × 10^9/L on Day 5 or for all patients with a peak WBC count ≥16 × 10^9/L. Patients with WBC > 7 × 10^9/L on Day 3 have a higher risk of ED. Leukocyte proliferation is associated with TNF-α rather than IL-6, and TNF-α may be a potential biomarker for predicting ED. [ABSTRACT FROM AUTHOR]

Background: Cuproptosis (copper death) is a recently found cell death type produced by copper iron; nonetheless, the properties of cuproptosis molecular subtypes and possible involvement of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) in ovarian cancer (OC) remain unknown. Methods: CRG changes were characterized at the genomic and transcriptional levels in 656 OC samples, and their expression patterns were investigated using three different datasets. Results: We identified three distinct molecular subtypes, and discovered that variations in molecular subtypes were linked to patient prognosis, TME cell infiltration characteristics, malignancy, and immune-related pathways. Then, in order to predict overall survival (OS), we created a risk score and tested its predictive potential in OC patients. As a result, we created a very accurate nomogram to increase risk score clinical applicability. Better OS, younger age, early stage, and immune activity were all associated with a low risk score. The hallmarks of a high-risk score are older age, advanced stage, immunosuppression, and a bad prognosis. Furthermore, risk score was linked to immune checkpoint expression (including PD-L1, CTLA4), targeted therapy gene expression (PARP, PDGFRA), cancer stem cell (CSC), chemotherapy and targeted medication sensitivity. Conclusions: Our comprehensive analysis of CRGs in OC showed their potential role in TME, clinicopathological characteristics, chemotherapy and targeted drug screening and prognosis. These discoveries could help us better understand CRGs in OC, as well as pave the path for novel ways to assess prognosis and design more effective immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Identifying new prognostic markers can provide a reference for the treatment of lung adenocarcinoma (LUAD) to improve its prognosis. Circadian rhythm disturbances are closely linked to the initiation, progression and prognosis of lung cancer. We aimed to explore the value of circadian miRNA (cmiRNA) as a prognostic marker of LUAD. A prognostic signature comprising seven pairs of cmiRNAs was established, and it exhibited excellent predictive value for overall and progression-free survival. High-risk patients showed higher sensitivity to primary chemotherapy drugs and targeted medicine compared with low-risk patients. Overall, the novel circadian-related miRNA pair signature could provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for LUAD. The cmiRNA–Cgenes network and corresponding enrichment analysis might provide clues for studying the underlying circadian dysregulation mechanisms involved in the progression of LUAD in the future. Lung adenocarcinoma (LUAD) is the primary histological subtype of lung cancer with a markedly heterogeneous prognosis. Therefore, there is an urgent need to identify optimal prognostic biomarkers. We aimed to explore the value of the circadian miRNA (cmiRNA) pair in predicting prognosis and guiding the treatment of LUAD. We first retrieved circadian genes (Cgenes) from the CGDB database, based on which cmiRNAs were predicted using the miRDB and mirDIP databases. The sequencing data of Cgenes and cmiRNAs were retrieved from TCGA and GEO databases. Two random cmiRNAs were matched to a single cmiRNA pair. Finally, univariate Cox proportional hazard analysis, LASSO regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature consisting of seven cmiRNA pairs. The signature exhibited good performance in predicting the overall and progression-free survival. Patients in the high-risk group also showed lower IC50 values for several common chemotherapy and targeted medicines. In addition, we constructed a cmiRNA–Cgenes network and performed a corresponding Gene Ontology and Gene Set enrichment analysis. In conclusion, the novel circadian-related miRNA pair signature could provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for LUAD. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis investigated the relationships between the CD44+/CD24− phenotype and tumor size, lymph node metastasis, distant metastasis, disease-free survival (DFS), and overall survival (OS) in 8036 postoperative breast cancer patients enrolled in 23 studies. Methods: A literature search of PubMed, Medline, Cochrane, Embase, and PMC was conducted to identify eligible studies. The combined odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed to evaluate the relationships between the CD44+/CD24− phenotype and the pathological and biological characteristics of breast cancer patients, and the combined hazard ratios (HRs) and 95% CIs were calculated to evaluate the relationships between CD44+/CD24− and DFS and OS of breast cancer patients using Stata12.0 software. Results: The CD44+/CD24− phenotype were not related to the tumor size (tumor size > 2.0 vs ≤ 2.0 cm, combined OR = 0.98, 95% CI 0.68–1.34, p = 0.792) and did not promote lymph node metastasis (lymph node metastasis vs. no lymph node metastasis, OR = 0.92, 95% CI 0.67–1.27, p = 0.626) and distant metastasis (distant metastasis vs no distant metastasis, combined OR = 3.88, 95% CI 0.93–16.24, p = 0.064). The CD44+/CD24− phenotype was negatively correlated with postoperative DFS (HR = 1.67, 95% CI 1.35–2.07, p < 0.00001) and OS (combined HR = 1.52, 95% CI 1.21–1.91, p = 0.0004). Conclusion: These results suggested expression of the CD44+/CD24− phenotype cannot be used as a reliable indicator of the tumor size, lymph node metastasis, and distant metastasis, however, it can be used be a potential therapeutic targets of DFS, OS in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Atypical/unbalanced rearrangement in salivary secretory carcinoma was observed and its incidence, patterns, and clinical significance remain unknown. Methods: One hundred and ninety-six cases of diagnosed secretory carcinoma were retrospectively reviewed. Fluorescence in situ hybridization for NTRK3/ ETV6::NTRK3 was conducted on cases carrying the atypical ETV6 fluorescence in situ hybridization signals. Cases without ETV6::NTRK3 were selected for nextgeneration sequencing to reveal novel partner. Immunohistochemistry and follow-up were performed. Results: Twenty-seven cases were confirmed to carry the atypical ETV6 fluorescence in situ hybridization signal patterns. The most common type of abnormality was the duplication of ETV6 50 end (1Y1GnR, n ≥ 2) with the incidence of 81.5% (22/27). Seventeen of 19 were identified with ETV6::NTRK3 and 2 with ETV6::RET. The immunophenotype was similar to the typical secretory carcinoma group. TrkC exhibited 68.8% sensitivity and 100% specificity for NTRK3 fusion. Microscopically, 5 out of 21 were accompanied by necrosis and 3 out of 21 showed neural invasion. Four out of 19 patients showed local relapse, 2 developed distant metastasis, and 1 died of disease. The patients with distant metastasis and even dead were both harbored ETV6::RET rearrangement. Statistical analysis revealed that there were no significant differences in disease-free survival, relapse-free survival, and distant metastasis-free survival between atypical and typical groups. Conclusion: Gene rearrangement can be identified although the fluorescence in situ hybridization signals were atypical, which was instructive for secretory carcinoma diagnosis in clinical practice. The signals of partners were also always atypical which may have an impact to the efficacy of targeted drugs. There was no statistical evidence that this group possessed worse prognosis. However, secretory carcinomas with ETV6::RET have dismal prognosis than those with ETV6::NTRK3. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common gastrointestinal tumor with a poor prognosis, which is associated with poor differentiation of tumor cells. However, the potential value of cell differentiation-related molecules in predicting the benefit and prognosis of immune checkpoint inhibitors (ICI) therapy remains unknown. Herein, to investigate the differentiation trajectory of HCC cells and their clinical significance, a differentiation-related gene prognostic index (DRGPI) based on HCC differentiation-related genes (HDRGs) was constructed to elucidate the immune characteristics and therapeutic benefits of ICI in the HCC subgroup defined by DRGPI. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from four HCC samples were integrated for bioinformatics analysis. Then, PON1, ADH4, SQSTM1, HSP90AA1, and STMN1 were screened out to construct a DRGPI. More intriguingly, RT-qPCR validation of the expression of these genes yielded consistent results with the TCGA database. Next, the risk scoring (RS) constructed based on DRGPI suggested that the overall survival (OS) of the DRGPI-high patients was significantly worse than that of the DRGPI-low patients. A nomogram was constructed based on DRGPI-RS and clinical characteristics, which showed strong predictive performance and high accuracy. The comprehensive results indicated that a low DRGPI score was associated with low TP53 mutation rates, high CD8 T cell infiltration, and more benefit from ICI therapy. Homoplastically, the high DRGPI score reflected the opposite results. Taken together, our study highlights the significance of HCC cell differentiation in predicting prognosis, indicating immune characteristics, and understanding the therapeutic benefits of ICI, and suggests that DRGPI is a valuable prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

Limited studies have interrogated the genomic landscape of Chinese melanoma in which acral and mucosal melanoma are the mainstay. In this study, we carried out a retrospective analysis on 81 Chinese melanoma patients (15 acral, 25 mucosal and 41 cutaneous melanoma). With the identification of 1114 mutations spanning 248 genes, we summarized that the mutation spectrum varied significantly by subtypes. Acral melanoma and mucosal melanoma had significantly more CNVs. MYC amplification was one of the most commonly detected CNVs, other frequent CNVs in mucosal melanoma included NBN and KDR, which were associated with the poor survival of melanoma patients. A generally low TMB, with a median of only 5.1 mut/Mb, was observed in three groups including cutaneous melanoma. Additionally, over 50% variants in DNA damage repair pathway were detected in all three subtypes, most of which were HRD related genes. Patients with alterations of HRD related genes had a longer survival time after immunotherapy. This study revealed a molecular profiling of Chinese patients with advanced melanoma, and proposed the high variant rate in DDR pathway as a biomarker of immunotherapy, which might provide therapeutic targets and guidance in making clinical decision for different Chinese melanoma. [ABSTRACT FROM AUTHOR]

Background: Activating transcription factor-2 (ATF2) is a member of the basic leucine zipper family of DNA-binding proteins, which exhibits both oncogenic and tumor suppression activity in different tumors. However, the molecular mechanism of its dual function in cancer chemotherapy especially in gastric cancer has still not been elucidated. Methods: The protein expression and location of ATF2 in gastric cancer tissues was detected with immunohistochemistry assay, and the clinical significance was analyzed using TCGA and GEO database. The activation and impact of ATF2 in cisplatin treated cells were evaluated with western blot, incucyte live cell analysis, clone formation and tumor xenografts assays. Interaction between ATF2 and p53 was confirmed with immunoprecipitation and GST-pull down. Potential molecular mechanism of ATF2 in different p53 status cells was analyzed with RNA sequencing and real-time quantitative PCR. Results: ATF2 mainly located in the nucleus of cancer cells, higher ATF2 level was associated with poor five-year survival of gastric patients, especially in those undergone chemotherapy treatment. Cisplatin treatment significantly activated ATF2 in p53 mutant cells. ATF2 could interact with the trans-activation domain of p53 and enhance cisplatin sensitivity in p53 wild type cell lines, while promoted cell survival in mutant p53 cancer cells by affecting ERK1/2 pathway. Conclusions: This study confirmed the effect of ATF2 on cisplatin sensitivity was associated with the functional status of p53 in gastric cancer cells. Integrated analysis of ATF2 expression and P53 status could be used to evaluate the chemotherapy sensitivity and prognosis of gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNA P73 antisense RNA 1 T (non-protein coding), also known as Lnc RNA TP73-AS1, is dysregulated in various tumors but the correlation between its expression and clinicopathological parameters and/or prognoses in cancer patients is inconclusive. Here, we performed a meta-analysis to evaluate the prognostic value of Lnc RNA TP73-AS1 for malignancies.Methods: We systematically searched four online databases including PubMed, the Web of Science, Embase, and the Cochrane Library for eligible articles published up to June 29/2020. Odds ratios (ORs) and Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the association of TP73-AS1 expression with prognostic and clinicopathological parameters. We further validated TP73-AS1 expression in various malignancies and its potential prognostic value using the GEPIA online database. We predicted potential biological processes and relevant signal mechanisms through the public databases.Results: A total of 26 studies examining 14 cancers were analyzed to evaluate the relationship between TP73-AS1 expression, clinicopathological features and prognostic indicators. The results indicated that TP73-AS1 expression markedly correlates with TNM stage (OR = 3.27,95% CI:2.43-4.39, P < 0.00001), tumor size (OR = 3.00, 95%CI:2.08-4.35, P < 0.00001), lymph node metastasis (OR = 2.77, 95%CI:1.42-5.38,P < 0.00001) and distant metastasis (OR = 4.50,95%CI:2. 62-7.73,P < 0.00001). No correlation with age (OR = 1.12,95%CI:0.77-1.64, P > 0.05), gender (OR = 1.08, 95%CI:0.84-1.38, P > 0.05) or differentiation (OR = 1.39, 95%CI:0.71-2.70, P = 0.340) was observed. TP73-AS1 overexpression was a biomarker of poor Overall survival(OS)(HR = 1.85,95%CI:1.53-2.22, P < 0.00001) and Disease-Free-Survival (DFS) (HR = 1.57,95%CI:1.03-2.42, P < 0.05). Dysregulated TP73-AS1 expression and its prognostic value in various cancers was validated based on The Cancer Genome Atlas (TCGA). Further biological function predictions indicated that TP73-AS1 was involved in pro-oncogenic signaling.Conclusions: The upregulation of Lnc RNA TP73-AS1 was related to detrimental clinicopathological parameters and can be considered an indicator of poor prognosis for cancer malignancies. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the impact of AAD on the severity and mortality of COVID-19 patients and compare clinical outcomes between patients with and without AAD. Methods: In the systematic review and meta-analysis, we searched PubMed, Embase, Web of Science for studies reporting allergic rhinitis, asthma prevalence in COVID-19 patients and compared clinical outcomes, and excluded duplicate publications, reviews, comments, single or few cases reports (< 100 cases). We determined the pooled effect estimates using random effect model. Results: Thirty-four studies (345,091) were finally included for the meta-analysis. On the basis of 32 studies (337,821) involving with the severity of COVID-19, we did not find significant association between AAD and the severity of COVID-19 (p = 0.35, OR 1.10, 95% CI 0.90–1.35). Subgroup analysis indicated there was no the variability in the prevalence of AAD among COVID-19 patients in different study designs, disease categories, countries, the definition of severity, and population size of AAD. Based on 21 studies (306,331) involving with the mortality of COVID-19, AAD was significantly associated with the decreased mortality of COVID-19 (p < 0.05, OR 0.83, 95% CI 0.70–0.99). The subgroup analysis showed AAD was not associated with the mortality of COVID-19 in different countries or regions. Based on the population size of AAD, we found AAD within 100 cases was not associated with the mortality of COVID-19 (p = 0.63, OR 1.15, 95% CI 0.65–2.03). Moreover, study design was possible heterogeneity source as the heterogeneity I2 was reduced to 0 in prospective studies. Conclusion: The preexisting AAD was not inclined to deteriorate the course of COVID-19. The prevalence of AAD was not associated with the severity of COVD-19 patients and inclined to be significantly associated with the decreased mortality risk of COVID-19. [ABSTRACT FROM AUTHOR]

Immunosenescence refers to the immune system undergoing a series of degenerative changes with advancing age and is tightly associated with the initiation and progression of cancers. However, the immunosenescence-related genes as critical biomarkers for bladder cancer (BLCA) have not been systematically analyzed. We retrieved the immunosenescence-related genes from the public database and verified their association with hallmarks of immunosenescence based on The Cancer Genome Atlas (TCGA) cohort. Through gene pairing, Lasso, and univariate Cox regression, an 8-gene pair model was constructed to evaluate the overall survival of BLCA, which was then validated in the training cohort (P < 0.001 , n = 396), two external validation cohorts (P < 0.05 , n = 165 ; P < 0.001 , n = 224), and local samples (P < 0.05 , n = 10). We also downloaded the clinical information and gene expression matrices of other 32 different cancers from TCGA. The established model showed significant predictive value for the prognosis in 15 cancers (P < 0.05). The risk model could also serve as a promising predictor for immunotherapeutic response, which has been verified by the TIDE algorithm (P < 0.05), IMvigor210 dataset (P < 0.01 , n = 298), and other two datasets correlated with immunotherapy (P < 0.05 , n = 56 ; P = 0.17 , n = 27). The TCGA dataset, in vitro cell experiments, and pan-cancer analysis displayed that the gene signature was associated with cisplatin sensitivity (P < 0.05). Overall, we proposed a novel immunosenescence-related gene signature to predict prognosis, immunotherapeutic response, and cisplatin sensitivity of BLCA, which were validated in different independent cohorts, local samples, and pan-cancer analyses. [ABSTRACT FROM AUTHOR]

Many studies have revealed the crucial roles of miRNA in multiple human cancers, including lung adenocarcinoma (LUAD). In this study, we sought to explore new miRNA-mRNA pairs that are associated with LUAD prognosis. A novel miRNA-mRNA regulatory network associated with prognosis in LUAD was identified and validated using the bioinformatic tools including OncomiR database, StarBase, miRnet, GEPIA2, UALCAN. Twenty key miRNAs were compiled after the analysis of the expression and prognostic value in OncomiR and StarBase. Targeted mRNAs of these key miRNAs were predicted in miRnet, and the resulting mRNAs were also analyzed for their prognostic values and expression patterns in GEPIA2 and UALCAN, respectively. Further expression correlation analysis was performed in StarBase. Subsequently, a new miRNA-mRNA network was built, of which each RNA pair showed negative expression correlation, opposite expression pattern, and prognostic value. Protein-protein interaction network was under construction for the mRNAs, and 19 hub genes were determined. Enrichment analysis showed that "Cell Cycle, Mitotic" was the most significantly enriched term. Then, a miRNA-hub gene sub-network was built. We selected and validated the regulatory relationship of some miRNA-hub pairs, including hsa-miR-1976/RFC2, hsa-let-7c-5p/RFC2, hsa-let-7c-5p/ESPL1, hsa-let-7c-5p/CDC25A, and hsa-miR-101-3p/KIF2C. Moreover, over-expression of hsa-miR-1976 and hsa-let-7c-5p resulted in significant cell cycle arrest. Our results determined new prognosis-associated miRNA-mRNA pairs and might shed further light on the mechanism via which miRNA-mRNA network influences prognosis in LUAD. [ABSTRACT FROM AUTHOR]

• IL-7 and TNF-α are risk factors for short-term mortality in elderly septic patients. • IL-7 is correlated with TNF-α but not with the severity of symptoms in sepsis. • Combination of IL-7 and other factors can be used in precision medicine for sepsis. The identification of novel prognostic biomarkers in elderly septic patients are essential for the improvement of mortality in sepsis in the context of precision medicine. The purpose of this study was to explore the expression pattern and prognostic value of serum interleukin-7 (IL-7) in predicting 28-day mortality in elderly patients with sepsis. Patients were retrospectively enrolled according to the sepsis-3.0 diagnostic criteria and divided into the survival group and non-survival group based on the clinical outcome at the 28-day interval. The baseline characteristic data, samples for the laboratory tests, and the SOFA, Acute Physiology and Chronic Health Evaluation (APACHE II), as well as Glasgow coma scale (GCS) scores, were recorded within 24 h after admission to the emergency department. Serum levels of IL-7 and TNF-α of the patients were quantified by the Luminex assay. Spearman correlation analysis, logistic regressive analysis and receiver operating characteristic curve (ROC) analysis were performed, respectively. Totally, 220 elderly patients with sepsis were enrolled, 151 of whom died in a 28-day period. Albumin (ALB), high-density lipoprotein (HDL), systolic pressure (SBP), and platelet (PLT) were found to be significantly higher in the survival group (p < 0.05). IL-7 was shown to be correlated with TNF-α in the non-survival group (p = 0.030) but not in the survival group (p = 0.194). No correlation was shown between IL-7 and other factors (p > 0.05). IL-7 and TNF-α were found to be independent risk factors associated with the 28-day mortality (OR = 1.215, 1.420). Combination of IL-7, SOFA and ALB can make an AUROC of 0.874 with the specificity of 90.77 %. Combination of IL-7 and TNF-α can make an AUROC of 0.901 with the sensitivity of 90.41 % while the combination of IL-7, TNF-α, and ALB can make an AUROC of 0.898 with the sensitivity of 94.52 %. This study highlights the importance of monitoring the serum level of IL-7 and TNF-α in elderly septic patients as well as evaluating the combinations with other routine risk factors which can be potentially used for the identification of elderly septic patients with higher risk of mortality. [ABSTRACT FROM AUTHOR]

Objective: A systematic review and meta-analysis were performed to evaluate the prevalence and prognosis of otorhinolaryngological symptoms in patients with the diagnosed coronavirus disease 2019 (COVID-19). Methods: A systematic search of PubMed, Embase, Web of Science, and Google Scholar databases was performed up to August 19, 2020.We included studies that reported infections with COVID-19 and symptoms of otolaryngology. The retrieved data from the respective studies were evaluated and summarized. The study's immediate result was to assess the combined prevalence of otorhinolaryngological symptoms in patients with COVID-19. However, the secondary result was to determine the exacerbation of COVID-19 infection in patients with otorhinolaryngological symptoms. Results: Fifty-four studies with 16,478 patients were included. Olfactory dysfunction, sneezing and sputum production were the 3 most prevalent otorhinolaryngological symptoms in patients with COVID-19. The pooled prevalence amongst the prevalent symptoms was 47% (95% CI 29–65; range 0–98; I2 = 99.58%), 27% (95% CI 11–48; range 12–40; I2 = 93.34%), and 22% (95% CI 16–30; range 2–56; I2 = 97.60%), respectively. The proportion of severely ill patients with sputum production and shortness of breath was significantly higher among patients with COVID-19 infections (OR 1.66 [95% CI 1.08–2.54]; P = 0.02, I2 = 51% and 3.29 [95% CI 1.57–6.90]; P = 0.002, I2 = 49%, respectively). Subgroup analysis showed no statistically significant differences between the incidence of otolaryngology symptoms in severely ill patients and non-severely ill patients (OR 1.43 [95% CI 1.12–1.82]; P = 0.07 I2 = 53.1%). In contrast, the incidence of shortness of breath in severely ill patients was significantly increased (3.29 [1.57–6.90]; P = 0.002, I2 = 49%). Conclusion: Our research shows that otorhinolaryngology symptoms in patients with COVID-19 are not uncommon, which should attract otorhinolaryngologists' attention. [ABSTRACT FROM AUTHOR]

Peripherin-2 (PRPH2) is a transmembrane glycoprotein crucial for the morphogenesis and stabilization of the photoreceptor outer segments. Variations in PRPH2 gene are associated with vision-threatening diseases. Clinical manifestations and multimodal imaging were presented, as well as treatment history and six-year follow-up. In addition, genetic testing was performed to confirm the diagnosis. In this report, we present an extremely rare case of choroidal neovascularization (CNV) secondary to pattern dystrophy simulating fundus flavimaculatus (PDSFF). Multimodal imaging showed typical symmetric yellow flecks in posterior pole and choroidal neovascularization requiring timely treatment. A novel nonsense variant of c.552 C > G; p.Y184X in PRPH2 gene was detected. The patient received intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment and maintained a good vision after six years. We described a novel PRPH2 variant (Y184X) associated with PDSFF, its multimodal imaging, and long-term prognosis. Intravitreal anti-VEGF treatment can offer excellent visual prognosis in patients with PDSFF-associated CNV. [ABSTRACT FROM AUTHOR]

Introduction: The current framework for risk stratification is still insufficient for highly heterogeneous intermediate‐risk acute myeloid leukemia (IRC‐AML), which lacks specific genomic abnormalities. Methods: In order to incorporate novel biomarkers to refine current risk stratification strategies for patients with this subtype, we investigated pretreatment telomere length (TL), which is essential for maintaining genomic stability, in 204 adults with de novo AML (non‐acute promyelocytic leukemia). Results: We found that TL measured at diagnosis did not decrease with advancing age in 204 patients with AML (R2 = 0.001, P =.695). A multivariate analysis demonstrated that short TL was independently associated with an inferior relapse‐free survival (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.48‐6.41, P =.003); event‐free survival (HR 2.14, 95% CI 1.12‐4.08, P =.021); and overall survival (HR 2.26, 95% CI 1.09‐4.67, P =.028) in IRC‐AML patients. In addition, IRC‐AML patients with short TL also exhibited an increased cumulative incidence of hematologic relapse (HR 2.32, 95% CI 1.08‐5.26, P =.032). Conclusion: Short TL is an independent prognostic factor for poor prognosis in patients with IRC‐AML and may represent a novel mechanism that links genomic stability and disease progression. [ABSTRACT FROM AUTHOR]

Background: Uterine rhabdomyosarcoma is an extremely rare malignant tumor that usually affects young women and has a poor prognosis.Case Presentation: A 19-year-old nulliparous woman presented to the emergency department under sedation due to seizures. Imaging examination revealed cerebral venous thrombosis. During thrombolytic therapy, she developed vaginal bleeding followed by uterine inversion secondary to uterine rhabdomyosarcoma. The inverted uterus was mistaken for a cervical tumour and was removed vaginally. The patient's disease progressed despite chemotherapy with vincristine, actinomycin D and cyclophosphamide and she died within 6 months. To our knowledge, this is the first case of uterine rhabdomyosarcoma complicated with cerebral venous thrombosis.Conclusions: Malignancy is an important diagnostic in patients with cerebral venous thrombosis with no obvious cause. This case demonstrates the importance of considering uterine neoplasms in the differential diagnosis of adolescent girls with abnormal uterine bleeding. Further, careful anatomical evaluation of vaginal masses should be performed prior to surgical intervention. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy. Methods: Bioinformatics analysis of The Cancer Genome Atlas (TCGA), the NCBI Gene Expression Omnibus (GEO) database, USUC Xena database, cBioPortal for Cancer Genomics, and MethSurv were performed to examine the aberrant genetic pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. The regulation of ccRCC tumor cell lines proliferation by LRRK2 was examined by CCK8 assay. Results: Bioinformatics analysis showed that LRRK2 expression was up-regulated and largely correlated with DNA methylation in ccRCC. The up-regulation of LRRK2 was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage, and metastatic status of ccRCC patients. Meanwhile, Kaplan–Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; knockdown of LRRK2 expression attenuated the proliferation ability of ccRCC tumor cell lines; protein–protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR. Conclusion: We found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC. [ABSTRACT FROM AUTHOR]

The tight relationship between ferroptotic cell death and immune response demonstrated by recent studies enlightened us to detect the underlying roles of ferroptosis-related long noncoding RNAs (frlncRNAs) in the tumor microenvironment of bladder cancer (BCa). We collected 121 ferroptosis regulators from previous studies. Based on their expression values, 408 cases with BCa were clustered. The patients in different clusters showed diverse immune infiltration, immunotherapy response, and chemotherapy effectiveness, revalidating the tight correlation with ferroptosis and tumor immunity. Through differential, coexpression, Kaplan-Meier, Lasso, and Cox analysis, we developed a 22-lncRNA-pair signature to predict the prognosis of BCa based on gene-pair strategy, where there is no need for definite expression values. The areas under the curves are all over 0.8. The risk model also helped to predict immune infiltration, immunotherapeutic outcomes, and chemotherapy sensitivity. Totally, the prognostic assessment model indicated a promising predictive value, also providing clues for the interaction between ferroptosis and BCa immunity. [ABSTRACT FROM AUTHOR]

Although T‐cell receptors (TCRs) are related to the progression of breast cancer (BC), their prognostic values remain unclear. We downloaded the messenger RNA (mRNA) profiles and corresponding clinical information of 1413 BC patients from the Cancer Genome Atlas and Gene Expression Omnibus database, respectively. The different expression analysis of 104 TCRs in BC samples was performed, and the consensus clustering based on 104 TCRs was performed by using the K‐mean method of R language. Univariate cox regression analysis was used to screen TCRs significantly associated with the prognosis of BC, and LASSO Cox analysis was applied to optimize key TCRs. The risk score was calculated using the prognostic model constructed based on six optimal TCRs, and multivariate Cox regression analysis was used to determine whether it was an independent prognostic signature. Finally, the nomogram was constructed to predict the overall survival of BC patients. Six optimal TCRs (ZAP70, GRAP2, NFKBIE, IFNG, NFKBIA, and PAK5), which were favorable for the prognosis of BC patients, were screened. Risk score could reliably predict the prognosis of BC patients as an independent prognostic signature. In addition, when bringing into two independent prognostic signatures, age and risk score, the nomogram model could better predict the overall survival of BC patients. Our results suggested that the poor prognosis of BC patients with high risk might be due to an immunosuppressive microenvironment. In summary, a prognostic risk model based on six TCRs was established and could efficiently predict the prognosis of BC patients. [ABSTRACT FROM AUTHOR]

We investigated the risk factors for diffuse midline gliomas of the spinal cord (DMGSCs). Seventy patients with spinal cord gliomas in two hospitals were analyzed retrospectively. Sixty‐nine patients that underwent surgery achieved partial or gross total removal. The patients were subdivided into some groups, based on age, WHO grade, tumor location within the cord, tumor size, and molecular profile: immunohistochemical expression of p53 and ATRX, and mutational status of Histone 3 (H3), and BRAF. Thirty‐three patients had an H3 K27M mutation (47%). Some clinical characteristics were significantly different between H3 K27M mutant and H3 wild‐type tumors. The main risk factors for DMGSCs were male sex, glioblastomas, and ≤ 2 spinal cord segments. The median survival period of patients with H3 K27M mutant tumors was significantly shorter than those with H3 wild‐type tumors (17.0 ± 3.7 months vs censored, P < 0.0001). In the DMGSC subgroup, patients with thoracic cord tumors had a significantly better prognosis than those with cervical cord tumors (31.0 ± 6.0 vs 10.0 ± 4.8 months). Patients > 45 years of age survived significantly longer than patients < 19 years (P = 0.001). In conclusion, H3 K27M mutation significantly predicts a worse outcome of spinal cord gliomas. Anatomical location and age are the main risk factors for DMGSCs. [ABSTRACT FROM AUTHOR]

Acute liver injury (ALI) refers to abnormalities in liver function caused by various causes and accompanied by poor prognosis and high mortality. Common predisposing factors for the disease are viral hepatitis, bacteria, alcohol, and certain hepatotoxic drugs. Inflammatory response and oxidative stress are critical for the pathogenesis of ALI. Pterostilbene (Pte), a natural polyphenol product extracted from blueberries and grapes, has been reported that exerted multiple biological activities, including antioxidative, anti-inflammatory, anti-carcinogenic, and anti-apoptotic properties. However, there is very little data showing the hepatoprotective effect of Pte on lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced ALI in mice. In this study, the possible protective effect and potential mechanisms of Pte on ALI are being investigated. It has been found that Pte markedly ameliorates LPS/D-Gal-induced inflammatory infiltration, hemorrhage, and dissociation of the hepatic cord, reducing the myeloperoxidase (MPO) activity in liver tissues and serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in ALI. Pte also inhibits LPS/D-Gal-induced secretion of pro-inflammatory cytokine tumor necrosis factor-a (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β) in liver tissues. Furthermore, the western blot analysis reveals that LPS/D-Gal-activated nuclear factor-kappa B (NF-κB) is significantly inhibited by Pte, and nuclear factor (erythroid-derived 2)–like 2 (Nrf2) and heme oxygenase-1 (HO-1) are upregulated by Pte. In conclusion, our results suggest that Pte exerts anti-inflammatory and antioxidative effects, which might contribute to ameliorating LPS/D-Gal-induced ALI in mice. Pte has the potential to be a preventive hepatoprotective agent. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly malignant and common tumor. Many biomarkers have been identified for HCC. However, the available ones are not accurate enough in term of prognostic value and new markers are needed for the prognosis of this disease. Sirtuins are NAD(+)-dependent histone deacetylases involved in many biological processes of cancers, consisting of family members SIRT1-SIRT7. However, the prognostic value of the SIRTs in HCC remains largely unknown. Methods: Differential expression of SIRTs and survival analysis were assessed in patients with HCC using Oncomine and UALCAN databases. Gene set enrichment analysis (GSEA) was used for pathway analysis. Metascape software was used to construct gene ontologies, metabolic pathways and protein-protein interaction networks. Moreover, a HCC murine model was used to validate the expression levels of SIRT3/6/7 expression. Results: Differential expression analysis suggested that SIRT2-7, not SIRT1, were expressed at higher levels in HCC tissues compared to adjacent normal tissues. These SIRTs showed some similarities, as revealed by GO and KEGG pathway. Higher SIRT3/6/7 mRNA expression levels were found to be significantly associated with shorter overall survival (OS) in HCC patients. Both SIRT3/6/7 mRNA and protein levels were highly expressed in HCC. In addition, over-expression of SIRT3/6/7 was associated with tumor stage and grade in HCC patients. Univariate analysis showed that SIRT 6/7 expressions were linked to a shorter OS of HCC patients. Multivariate analysis showed that SIRT7 levels were independently associated with a significantly shorter OS in HCC patients. Conclusion: Differentially expressed SIRT3/6/7 were significantly associated with tumor stage, grade and OS in HCC patients. In addition, SIRT7 were independently associated with a significantly shorter OS in HCC patients. Thus, SIRT3/6/7 can be used as prognostic biomarkers to predict the survival of HCC patients. [ABSTRACT FROM AUTHOR]

Background: Mantle cell lymphoma (MCL) is an aggressive malignancy that accounts for 5– 10% of non-Hodgkin's lymphoma. MiRNA-223-3p has been demonstrated to be down-regulated in MCL and is a useful prognostic factor. However, little is known about underlying molecular mechanism of miRNA-233-3p in MCL. Methods: The expression levels of miRNA-223-3p and CHUK mRNA in MCL cells were detected by real-time quantitative PCR (RT-qPCR). The effects of miRNA-223-3p/CHUK overexpression/knockdown on MCL cell proliferation and apoptosis were measured by CCK-8 assay and annexin V PE/7-AAD-based flow cytometry/TUNEL assay, respectively. A nude mouse subcutaneous xenograft model was used to further evaluate the potential effects in vivo. Dual-luciferase reporter assay was used to verify the inhibitory effect of miRNA-223-3p on CHUK. Furthermore, the regulatory function of miRNA-223-3p on the CHUK/NF-ƘB2 axis was assessed by RT-qPCR, western blot and immunofluorescence. Results: In the present study, miRNA-223-3p overexpression inhibited proliferation and accelerated apoptosis of MCL cells in vitro and in vivo. The results of Luciferase reporter assay showed that CHUK was a direct target of miRNA-223-3p in HEK293T cells. Furthermore, the results of RT-qPCR, western blot confirmed that CHUK was targeted and negatively regulated by miRNA-223-3p for repressing NF-ƘB2 pathway activation in MCL cells. Importantly, CHUK overexpression promoted proliferation and suppressed apoptosis of MCL cells, whereas CHUK knockdown reversed down-regulated miRNA-223-3p -accelerated cell proliferation in vitro. Conclusion: In conclusion, miRNA-223-3p affects MCL development by regulating the CHUK/NF-ƘB2 signaling pathway, which is crucial to provide a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) could interact with each other to play a vital role in the pathogenesis of cancers. We aimed to examine the expression profile, clinical significance and regulatory relationship of miR-130a-3p and its predicted interactive lncRNA in clear cell renal cell carcinoma (ccRCC). Methods: Bioinformatics analysis was used to predict lncRNAs binding with miR-130a-3p. qRT-PCR was employed to detect the expression levels of miR-130a-3p and the miRNA-targeted lncRNA, and their clinical values in ccRCC were clarified. The lncRNA sponge potential of miR-130a-3p was assessed through dual-luciferase reporter assay and the biological effects of them were observed. Results: Colon cancer associated transcript 1 (CCAT1) directly interacted with miR-130a-3p and negatively regulated miR-130a-3p expression. CCAT1 was upregulated and miR-130a-3p was downregulated in ccRCC cell line and tissues (all P < 0.05). High CCAT1 and low miR-130a-3p expression was correlated with larger tumor size and advanced TNM stage in ccRCC patients. High CCAT1 level suggested a poor survival prognosis. There was a negative association between CCAT1 and miR-130a-3p expression (r = − 0.373, P = 0.010). MiR-130a-3p mimic and si-CCAT1 inhibited ccRCC cell proliferation and invasion, and induced apoptosis. Conclusions: CCAT1/miR-130a-3p axis may have potential to serve as a novel diagnostic and prognostic target of ccRCC patients. [ABSTRACT FROM AUTHOR]

Background: XPF (xeroderma pigmentosum complementation group F) is a key factor contributing to DNA damage excision of nucleotide excision repair pathway. The relationship between XPF expression and the risk and prognosis of colorectal cancer (CRC) is unclear. Methods: In this experiment, a total of 824 cases of colorectal tissue were collected. XPF protein expression was detected by immunohistochemical staining. We conducted a Mann–Whitney U test in order to explore the differential expression of XPF between CRC and non-cancer controls, and the correlation between XPF expression and CRC clinicopathological parameters. Univariate and multivariate Cox regression analyses were conducted to investigate the relationship between XPF expression and CRC prognosis. The Java based software GSEA as well as STRING, David, GO, KEGG were used to explore the function and regulation network of XPF. Results: The results demonstrated that the XPF expression in CRC was significantly up-regulated compared with non-tumor controls (P < 0.001) and adenoma tissue (P < 0.001). XPF protein was increased in the dynamic sequence of anal diseases to adenoma tissue to CRC. Expression of XPF was related to tumor location (P = 0.005) and tumor growth pattern (P = 0.009). The results of prognosis analysis suggested that in patients with stage T1-T2, XPF low expression may be significantly associated with better overall survival (HR = 7.978, 95% CI 1.208–52.673, P = 0.031). XPF and its interacting genes played a vital role in different processes of nucleotide excision repair pathway. XPF expression was related with Ubiquitin like protein specific protease activity. Conclusions: XPF might be a promising biomarker for CRC risk, and also showed potential as a prognostic predictor in CRC patients. [ABSTRACT FROM AUTHOR]

CerSs (ceramide synthases), a group of enzymes that catalyze the formation of ceramides from sphingoid base and acyl-CoA substrates. As far, six types of CerSs (CerS1-CerS6) have been found in mammals. Each of these enzymes have unique characteristics, but maybe more noteworthy is the ability of individual CerS isoform to produce a ceramide with a characteristic acyl chain distribution. As key regulators of sphingolipid metabolism, CerSs highlight their unique characteristics and have emerging roles in regulating programmed cell death, cancer and many other aspects of biology. However, the role of CerSs in lung cancer has not been fully elucidated. In this study, there was no significant change in the sequence or copy number of CerSs gene, which could explain the stability of malignant tumor development through COSMIC database. In addition, gene expression in lung cancer was examined using the OncomineTM database, and the prognostic value of each gene in non-small cell lung cancer (NSCLC) was analyzed by Kaplan-Meier analysis. The results showed that high mRNA expression levels of CerS2, CerS3, CerS4 and CerS5 in all NSCLC patients were associated with improved prognosis. Among them, CerS2 and CerS5 are also highly expressed in adenocarcinoma (Ade), but not in squamous cell carcinoma (SCC). In contrast, high or low expression of CerS1 and CerS6 no difference was observed in patients with NSCLC, Ade and SCC. Integrated the data of this study suggested that these CerSs may be a potential tumor markers or drug target of new research direction. [ABSTRACT FROM AUTHOR]

Background. Multiple studies have reported the significance of the systemic immune-inflammation index (SII) in the prognosis of colorectal cancer (CRC), but no consensus has yet been reached. The purpose of this study was to systematically assess the prognostic value of SII in patients with CRC. Materials and Methods. We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for eligible studies. The correlation between pretreatment SII and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in CRC patients was evaluated by combining the hazard ratio (HR) and 95% confidence interval (CI). Results. Twelve studies involving 3919 patients were included. Comprehensive analysis results showed that high SII indicated poor OS in CRC patients (HR = 1.777 , 95% CI: 1.328-2.376). Compared with patients with low SII values, patients with high SII had lower PFS (HR = 1.658 , 95% CI: 1.189-2.311). Subgroup analysis further verified the above results. Conclusions. SII may be a noninvasive and powerful tool for predicting survival outcomes in CRC patients. However, more well-designed studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Objective. To investigate the association between programmed death-ligand 1 (PD-L1) coupled with CD8+ tumor-infiltrating lymphocytes (TILS) and the clinicopathological features, along with prognosis of cervical squamous cell carcinoma (CSCC). Methods. 95 patients of CSCC received tumor resection at the Department of Pathology of the First Affiliated Hospital of University of Science and Technology of China (USTC) from 2015 to 2020. Full-automatic immunohistochemistry was applied to measure PD-L1 expression and CD8+ TILS density. Our literature deeply assessed the links between PD-L1 expression, clinicopathological features, and the influences of combination of PD-L1 and CD8+ TILS (PD-L1+/CD8+ TILS) on the prognosis of CSCC. Results. 64.21% of CSCC patients (61/95) expressed PD-L1, and PD-L1 expression was related to the Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, invasion depth, differentiation degree, metastasis of lymph node, and vascular invasion (P < 0.05). Dramatic correlation between PD-L1 expression and CD8+ TILS density was illustrated in CSCC patients (r = − 0.461 , P < 0.001). Obvious differences in differentiation degree, FIGO stage, infiltration depth, and lymph node metastasis were shown between patients with PD-L1 coupled with high-density of CD8+ TILS and those with PD-L1 coupled with low-density of CD8+ TILS (P < 0.05). Patients with PD-L1 negative expression exhibited better prognosis compared with those with PD-L1 positive expression (P < 0.05). Patients with PD-L1 coupled with high-density of CD8+ TILS showed better prognostic status, while those with PD-L1 coupled with low-density of CD8+ TILS had worse prognostic condition (P < 0.05). Differentiation, metastasis of lymph node, and FIGO stage were substantive impact elements of a CSCC patient's overall survival (OS) by Cox multivariate analysis. Conclusions. CD8+ TILS density is related to PD-L1 expression in carcinoma. PD-L1/CD8+ TILS density can be regarded as evaluation for the prognosis of patients with CSCC, providing a new therapeutic target in clinical application. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastric cancer is a prevalent malignant around the world. Aberrantly expression of microRNAs (miRNAs) contributes to the progression of tumors. The aim of this study was to investigate the expression and role of miR-892a in gastric cancer. METHODS: A total of 119 gastric cancer patients were enrolled in this study. And the expression of miR-892a in gastric cancer tissues and cells was measured using RT-qPCR analysis. Kaplan-Meier plotter and multivariate Cox regression analysis were used to explore the prognostic value of miR-892a in gastric cancer. The biological function of miR-892a in gastric cancer cells was evaluated using CCK-8 assays and Transwell assays. RESULTS: The expression of miR-892a was high-expressed in gastric cancer tissues and cells. The miR-892a expression was associated with tumor size, differentiation, lymph node metastasis, and TNM stages. Gastric cancer patients with high miR-892a expression showed a short overall survival rate. Overexpression of miR-892a promoted cell proliferation, migration, and invasion of gastric cancer cells. CONCLUSION: miR-892a was upregulated and predictor of poor prognosis in gastric cancer patients. The miR-892a in gastric cancer cells significantly promoted cell proliferative, migratory, and invasive properties. Furthermore, miR-892a may be served as a prognostic marker as well as a therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Objective To observe the expression changes of stimulator of interferon gene (STING), CC chemokine ligand 22 (CCL22), indoleamine-2, 3-dioxygenase (IDO)in the cervical cancer and to explore its clinical significance. Methods The surgically removed cervical cancer tissues and adjacent normal tissues from 83 cases of patients with cervical cancer were selected. The expression levels of STING, CCL22 and IDO were detected by RT-qPCR. The differences in STING, CCL22 and IDO expression between the cervical cancer tissues and adjacent normal tissues were compared. The relationship between the expression of STING, CCL22, IDO and the clinicopathological features of cervical cancer, as well as the relationship between the expression of STING, CCL22, IDO and the prognosis of cervical cancer were analyzed. Results The relative expression levels of STING, CCL22 and IDO were higher in the cervical cancer tissues than in the adjacent normal tissues (all P < 0.05). The relative expression of STING in the cervical cancer tissues was positively correlated with the relative expression of CCL22 and IDO (r = 0.707, r = 0.614, both P < 0.05), while the relative expression of CCL22 was positively correlated with the relative expression of IDO (r = 0.601, P < 0.05). The relative expression levels of STING, CCL22 and IDO in the cervical cancer tissues were related to FIGO stage and tissue differentiation degree (all P < 0.05), but not to age, pathological type, depth of myometrial invasion or lymph node metastasis (all P > 0.05). According to the critical value which was the mean expression of STING, CCL22 and IDO in the cervical cancer tissues, the patients were divided into the high expression and low expression groups of STING, CCL22 and IDO, respectively. Among them, there were 41 patients with high expression of STING and 42 patients with low expression of STING, 40 patients with high expression of CCL22 and 43 patients with low expression of CCL22, and 42 patients with high expression of IDO and 41 patients with low expression of IDO. The overall 3-year survival rate of patients with high expression of STING, CCL22 and IDO was lower than that of patients with low expression (χ² = 4.444, 8.201 and 5.449, respectively, all P < 0.05). Conclusion The high expression of STING, CCL22 and IDO in cervical cancer tissues is related to FIGO stage, tissue differentiation degree and patients' prognosis, which may synergetically promote the occurrence and development of cervical cancer. [ABSTRACT FROM AUTHOR]

Objective To study the expression and clinical significance of microRNA (miR)-200a-3p and GTPase activating protein SH3 domain binding protein 2 (G3BP2) in the gastric cancer tissues. Methods The expression of miR-200a-3p and G3BP2 in 97 cases of gastric cancer tissues and its paracancer tissues was detected by real-time quantitative PCR (qRT-PCR). The differencial expression of G3BP2 and miR-200a-3p and their relationships with clinicopatholog- ical features and prognosis were analyzed statistically. Results Compared with the paracancer tissues, the expression of miR-200a-3p was significantly lower in the gastric cancer tissues, while G3BP2 was significantly higher (both P < 0.05). There was a significant negative correlation between miR-200a-3p and G3BP2 in the cancer tissues (r = -0.634, P = 0.000). The expression of miR-200a-3p and G3BP2 in the cancer tissues was related to tumor TNM stage and tumor differentiation (all P < 0.05), but not related to gender, age, tumor size, location, infiltration depth or lymph node metastasis (all P > 0.05). The 3-year overall survival rate (OS) of patients with low miR-200a-3p expression was significantly lower than that of patients with high miR-200a-3p expression (P < 0.05). The 3-year OS of patients with high G3BP2 expression was significantly lower than that of patients with low G3BP2 expression (P < 0.05). Conclusion The expression of miR-200a-3p decreases in the gastric cancer tissues, while the expression of G3BP2 is elevated; the combined detection of them is helpful for the disease judgment and prognosis evaluation. [ABSTRACT FROM AUTHOR]

Background: Crescent formation in immunoglobulin A nephropathy (IgAN) has been demonstrated to be a risk factor for worse outcomes. For IgAN patients with 0–25% crescentic glomeruli (C1), whether corticosteroids (CS) can improve the prognosis remains unclear. We tried to investigate the need for using CS in IgAN patients with C1 in different proteinuria levels. Methods: A total of 120 eligible IgAN patients with C1 from two academic medical centers were retrospectively studied, and 57 (47.5%) received CS. Patients were grouped according to with or without CS. The outcomes were the rate of estimated glomerular filtration rate (eGFR) decline (ml/min per 1.73 m2/year) and a composite outcome (50% decrease in eGFR, end stage renal disease (ESRD) or death due to kidney disease). The progression of adverse outcome among them were analyzed in Kaplan–Meier curve. The independent significance of CS on renal outcome or eGFR decline rate were analyzed by multivariable Cox regression or linear regression. Results: Unadjusted Kaplan–Meier showed that the outcome of treated patients was better than that of the untreated patients. Multiple Cox regression and linear regression analysis found that CS independently protected the renal outcome and decreased the eGFR decline rate. In the subgroup analysis, multivariate linear regression showed that CS decreased the eGFR decline rate both in proteinuria ≥ 1 g/day and < 1 g/day. Conclusions: CS protected the renal outcome and slowed the eGFR decline rate of IgAN patients with C1, it also decreased the eGFR decline rate even in those with initial proteinuria < 1 g/day. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK- ALCL) is a definite entity in the WHO 2016 Classification that represents 2–3% of non-Hodgkin lymphoma (NHL) and 12% of T-cell NHL cases. ALK- ALCL lacks ALK protein expression, but expresses CD30 and has morphologic features similar to ALK positive anaplastic large cell lymphoma (ALK+ ALCL). Some studies indicate that ALK- ALCL and ALK+ ALCL possess different molecular and genetic characteristics. Besides, ALK- ALCL is worse than ALK+ ALCL in terms of treatment outcome, prognosis, and long-term survival. This review is aimed at summarizing information about ALK- ALCL, especially with respect to the treatment and prognosis. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome pathway is an important protein degradation regulatory system in cells. This pathway is also a reversible process that is strictly regulated, and the regulation of deubiquitinating enzymes (DUBs) represents an important facet of the process. Ovarian tumor-associated proteases domain-containing proteins (OTUDs), as a subfamily within the DUB family, serve an important role in regulatory mechanisms of several biological processes, through the regulation of gene transcription, cell cycle, immune response, inflammation and tumor growth processes, and may be important in the diagnosis of various diseases and constitute novel drug targets. However, the role of OTUDs in non-small-cell lung cancer (NSCLC) has not been fully elucidated. In the present study, the Oncomine database was used to examine gene expression in NSCLC, and the prognostic value of each gene was analyzed by Kaplan-Meier analysis. The results indicated that high mRNA expression levels of OTUD1, OTUD3, OTUD4 and putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 were associated with improved prognosis in all NSCLC and adenocarcinoma, but not in squamous cell carcinoma. By contrast, high expression levels of OTUD2 mRNA were associated with poorer overall survival in patients with NSCLC. These data suggested that these OTUD isozymes may be a potential drug target for NSCLC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the leading causes of cancer mortality in the world. P2X7 receptor (P2X7R), encoded by the P2rx7 gene, is a trimeric ion channel activated by extracellular Adenosine triphosphate and is widely expressed in various types of tissues and tumors to regulate inflammation, cell proliferation, or death. The discovery of new biomarkers and understanding the role of P2X7R in CRC are therefore critical to improving the prognosis and treatment of CRC. P2X7R expression was analyzed in CRC tumor samples and normal colorectal tissues from 97 patients and various colon cancer cell lines. The correlation of tumor antigens, survival periods, and P2X7R expression were documented. P2X7RHigh and P2X7RLow populations were observed in CRC patients. P2X7RHigh patients had relatively shorter survival periods, higher levels of serum carcinoembryonic antigen, and greater numbers of advanced tumors. In addition, P2X7R expression had a significant up-regulation in metastatic CRC and metastatic CRC cell lines, which indicates that P2X7R expression is positively associated with metastasis. P2X7R expression might be a potential biomarker for prognosis and metastasis of CRC. [ABSTRACT FROM AUTHOR]

Background: Activated neutrophils release depolymerized chromatin and protein particles into the extracellular space, forming reticular Neutrophil Extracellular Traps (NETs). This process is accompanied by programmed inflammatory cell death of neutrophils, known as NETosis. Previous reports have demonstrated that NETosis plays a significant role in immune resistance and microenvironmental regulation in cancer. This study sought to characterize the function and molecular mechanism of NETosis-correlated long non-coding RNAs (NCLs) in the prognostic treatment of liver hepatocellular carcinoma (LIHC). Methods: We obtained the transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and evaluated the expression of NCLs in LIHC. A prognostic signature of NCLs was constructed using Cox and Last Absolute Shrinkage and Selection Operator (Lasso) regression, while the accuracy of model was validated by the ROC curves and nomogram, etc. In addition, we analyzed the associations between NCLs and oncogenic mutation, immune infiltration and evasion. Finally, LIHC patients were classified into four subgroups based on consensus cluster analysis, and drug sensitivity was predicted. Results: After screening, we established a risk model combining 5 hub-NCLs and demonstrated its reliability. Independence checks suggest that the model may serve as an independent predictor of LIHC prognosis. Enrichment analysis revealed a concentration of immune-related pathways in the high-risk group. Immune infiltration indicates that immunotherapy could be more effective in the low-risk group. Upon consistent cluster analysis, cluster subgroup 4 presented a better prognosis. Sensitivity tests showed the distinctions in therapeutic effectiveness among various drugs in different subgroups. Conclusion: Overall, we have developed a prognostic signature that can discriminate different LIHC subgroups through the 5 selected NCLs, with the objective of providing LIHC patients a more precise, personalized treatment regimen. [ABSTRACT FROM AUTHOR]

Background: Membranous lupus nephritis (MLN) is a subepithelial immune deposition or its morphological sequelae with or without mesangial changes. Previous studies on the prognosis of MLN have shown relatively small sample sizes and short follow-up periods. Methods: Our study was a retrospective analysis of biopsy-proven MLN patients from January 2010 to January 2020 at Jinling Hospital in China. The clinical manifestations, pathological features, and renal outcomes of MLN patients were collected. The endpoint was defined as end-stage kidney disease (eGFR≤15 mL/min·1.73 m2 or need for renal replacement therapy) or a doubling of serum creatinine or an eGFR decline of more than 40%. We used Cox regression to analyze the risk factors for renal outcome and Kaplan–Meier curves were used to analyze renal survival rate. Results: In the total of 2884 lupus patients, we screened 535 MLN patients. 456 MLN patients were recruited with an average age of 34 ± 12 years, 87.8% for female patients and 62.1% patients of nephrotic syndrome with proteinuria of 2.67 g/24h. After follow-up of 78 (IQR, 47.3–113.0) months, 37 (8.1%) patients reached the renal endpoint. The 5-year and 10-year renal survival rates were 95.8% and 89.4%, respectively. 370 patients (81.1%) achieved complete remission, 43 patients (9.4%) had partial remission, and only 43 had no response. 34.4% MLN experienced a relapse. The Cox regression showed the risk factors that affect the renal prognosis include male, hypertension history, anemia, high uric acid, acute kidney injury, and interstitial fibrosis in the renal pathology. Conclusions: MLN mostly manifested as nephrotic syndrome, with few renal dysfunctions. Although MLN had a high relapse rate, most patients had a response to immunosuppressants and had a good renal outcome. [ABSTRACT FROM AUTHOR]