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Objective: The prognostic value of C-reactive protein to albumin ratio (CAR) has been identified in several cancers but not in extranodal natural killer T-cell lymphoma (ENKTL) as yet. We aimed to evaluate the prognostic value of CAR in ENKTL. Methods: A retrospective study with 246 patients with ENKTL was performed to determine the prognostic value of pretreatment CAR and examine the prognostic performance of CAR incorporating with International Prognostic Index (IPI) or natural killer/T-cell lymphoma prognostic index (NKPI) by nomogram. Results: The Cox regression analyses showed that high CAR (>0.3) independently predicted unfavorable progression-free survival (PFS, P =.011) and overall survival (OS, P =.012). In the stratification analysis, the CAR was able to separate patients into different prognoses regarding both OS and PFS in Ann Arbor stage I+II as well as III+IV, IPI score 0 to 1, and NKPI score 1 to 2 subgroups (all P <.05). Additionally, the predictive accuracy of the IPI-based nomogram incorporating CAR, albumin to globulin ratio (AGR), and IPI for OS and PFS appeared to be lower than the NKPI-based nomogram incorporating CAR, age, AGR, extranodal site, and NKPI. Conclusion: Pretreatment CAR is a simple and easily accessible parameter for independently predicting OS and PFS in patients with ENKTL. [ABSTRACT FROM AUTHOR]

Background: As the most common form of lymphoma, diffuse large B-cell lymphoma (DLBCL) is a clinical highly heterogeneous disease with variability in therapeutic outcomes and biological features. It is a challenge to identify of clinically meaningful tools for outcome prediction. In this study, we developed a prognosis model fused clinical characteristics with drug resistance pharmacogenomic signature to identify DLBCL prognostic subgroups for CHOP-based treatment.Methods: The expression microarray data and clinical characteristics of 791 DLBCL patients from two Gene Expression Omnibus (GEO) databases were used to establish and validate this model. By using univariate Cox regression, eight clinical or genetic signatures were analyzed. The elastic net-regulated Cox regression analysis was used to select the best prognosis related factors into the predictive model. To estimate the prognostic capability of the model, Kaplan-Meier curve and the area under receiver operating characteristic (ROC) curve (AUC) were performed.Results: A predictive model comprising 4 clinical factors and 2 pharmacogenomic gene signatures was established after 1000 times cross validation in the training dataset. The AUC of the comprehensive risk model was 0.78, whereas AUC value was lower for the clinical only model (0.68) or the gene only model (0.67). Compared with low-risk patients, the overall survival (OS) of DLBCL patients with high-risk scores was significantly decreased (HR = 4.55, 95% CI 3.14-6.59, log-rank p value = 1.06 × 10-15). The signature also enables to predict prognosis within different molecular subtypes of DLBCL. The reliability of the integrated model was confirmed by independent validation dataset (HR = 3.47, 95% CI 2.42-4.97, log rank p value = 1.53 × 10-11).Conclusions: This integrated model has a better predictive capability to ascertain the prognosis of DLBCL patients prior to CHOP-like treatment, which may improve the clinical management of DLBCL patients and provide theoretical basis for individualized treatment. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma is the most malignant tumor of the central nervous system. Several prediction models have been produced to aid in prognosis assessment. Age, a primary decision factor for prognosis, is associated with increased genomic alterations, however the exact link between increased age and poor prognosis is unknown. Objective: In this study, we aimed to reveal the underlying cause of poor prognosis in elderly patients. Methods: This study included data on 616 primary GBM tumor samples from the CGGA and TCGA databases and 41 nontumor brain tissue samples obtained from GSE53890. Hallmarks and clinicopathological characteristics were evaluated in both tumor and nontumor brain tissues. The association between choice of treatment regimen and age was measured using ANOVA and Student's t test. Results: Age was a robust predictor of poor prognosis in glioma. No age‐related hallmarks of cancer were detected, including pathological characteristics or mutations. However, treatment choice was strongly significantly different between old and young patients. Combined chemo‐radiation therapy could benefit old and young GBM patients, however, old patients are currently less likely to choose it. Conclusion: The vast divergence in prognosis between young and old GBM patients is largely caused by choice of treatment rather than age‐related tumor genomic characteristics. Postoperative standard radio‐ and chemotherapy provide strong benefits to primary glioblastoma patients of all ages. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, chemotherapy-induced interstitial pneumonitis (CIIP) is rare, but it has a high mortality. It has been reported that pegylated liposomal doxorubicin (PLD) may induce interstitial pneumonitis in some cases. However, the relationship between PLD and CIIP in breast cancer is still unknown. This study aims to investigate the incidence of PLD-induced interstitial pneumonitis in breast cancer patients.Methods: All cases of breast cancer with chemotherapy are collected in our hospital from January 2016 to October 2018, and 354 eligible patients were included in analysis. Patients were divided into two groups according to different chemotherapy regimens received: epirubicin plus cyclophosphamide with or without docetaxel (EC/EC-T group) and PLD plus cyclophosphamide with or without docetaxel (DC/DC-T group). Patients' general information and clinical characteristics, as well as the incidence of interstitial pneumonitis were compared between the two groups.Results: The symptomatic interstitial pneumonitis occurred in 12 patients who received DC/DC-T treatment with an incidence of 12.25% (12/98), while no interstitial pneumonitis occurred in EC/EC-T group (p < 0.001). Of the 12 patients, 4 patients developed interstitial pneumonitis after 3 cycles of chemotherapy,7 patients after 4 cycles and 1 patient after 5 cycles. The mean interval between the beginning of chemotherapy and the onset of CIIP was 3.75 cycles.Conclusion: Clinicians should pay attention to CIIP in breast cancer patients who receive more than three cycles of chemotherapy regimens containing pegylated liposomal doxorubicin plus cyclophosphamide with or without docetaxel. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the clinical characteristics and prognostic factors in Chinese patients with classical Hodgkin's lymphoma (cHL) involving extranodal sites. Methods: Clinical features and outcomes of 68 patients diagnosed with cHL involving extranodal sites from April 2003 to November 2017 were analyzed retrospectively. The data was compared with that of 76 cHL patients without extranodal involvement in the same period. Results: (1) Extranodal involvement was common in Chinese cHL patients. The most common sites were lung (44.1%) and bone (33.8%), followed by bone marrow, liver, pericardium, pleura and other sites. (2) With a median follow-up period of 4.58 years, the 5-year overall survival (OS) of 68 patients with extranodal involvement was significantly poorer than that of 76 patients with only nodal involvement (81.4% vs. 92.8%, p = 0.018). (3) In univariate analysis, lymphocytopenia (p = 0.027), elevated lactate dehydrogenase (LDH) (p = 0.026) and involved lymph node region (LNR) ≥4 (p = 0.044) predicted inferior freedom from progression (FFP) with significant difference. Elder age (p = 0.010), elevated LDH (p = 0.013), elevated platelet (p = 0.044), involved LNR ≥ 4 (p = 0.047) were also statistically significant in OS. Extranodal sites and number of extranodal sites showed no significant difference in FFP and OS. Factors with p-value smaller than 0.100 were evaluated in multivariate analysis, turning out that lymphocytopenia was the only independent adverse prognostic factor in FFP (p = 0.039; HR = 2.595) and OS (p = 0.028; HR = 4.993). Conclusion: Extranodal involvement was frequent in Chinese cHL patients, with lung to be the most commonly involved site. Lymphocytopenia was the only independent adverse prognostic factor. [ABSTRACT FROM AUTHOR]

To investigate the role of soluble programmed cell death ligand 1 (sPD-L1) protein in plasma of patients with Peripheral T-cell lymphoma (PTCL). In total, 80 patients with newly diagnosed PTCL and 75 healthy controls were enrolled. Levels of sPD-L1 were measured by ELISA at diagnosis and after 3–8 courses of chemotherapy. The expression of PD-L1 in tumor tissues from nine PTCL patients was also detected. sPD-L1 was higher in PTCL patients at diagnosis compared to healthy subjects (P < 0.0001). Patients in the intermediate/high-risk disease group had a higher level of sPD-L1 than patients in the low-risk group (P = 0.0003). Elevated sPD-L1 (≥176.30 pg/ml) was the only biomarker for PTCL that retain statistical significance in multivariate analysis. Patients in the low-risk group with sPD-L1 ≥ 176.30 pg/ml had an adverse prognosis. Histological analysis showed that the expression of PD-L1 in tissues was positively correlated with sPD-L1 levels in plasma (Spearman = 0.9177, P = 0.0013). sPD-L1 is a sensitive biomarker predicting clinical outcomes in PTCL. [ABSTRACT FROM AUTHOR]

Background: To reveal roles of reactive oxygen species (ROS) status in chemotherapy resistance and to develop a ROS scoring system for prognosis prediction in ovarian cancer.Methods: We tested the sensitizing effects of ROS elevating drugs to cisplatin (cDDP) in ovarian cancer both in vitro and in vivo. A ROS scoring system was developed using The Cancer Genome Atlas (TCGA) database of ovarian cancer. The associations between ROS scores and overall survival (OS) were analyzed in TCGA, Tothill dataset, and our in-house dataset (TJ dataset).Results: ROS-inducing drugs increased cisplatin-induced ovarian cancer cell injury in vitro and in vivo. ROS scoring system was established using 25 ROS-related genes. Patients were divided into low (scores 0-12) and high (scores 13-25) score groups. Improved patient survival was associated with higher scores (TCGA dataset hazard ratio (HR) = 0.43, P < 0.001; Tothill dataset HR = 0.65, P = 0.022; TJ dataset HR = 0.40, P = 0.003). The score was also significantly associated with OS in multiple datasets (TCGA dataset r2 = 0.574, P = 0.032; Thothill dataset r2 = 0.266, P = 0.049; TJ dataset r2 = 0.632, P = 0.001) and with cisplatin sensitivity in ovarian cancer cell lines (r2 = 0.799, P = 0.016) when used as a continuous variable. The scoring system showed better prognostic performance than other clinical factors by receiver operating characteristic (ROC) curves (TCGA dataset area under the curve (AUC) = 0.71 v.s. 0.65, Tothill dataset AUC = 0.73 v.s. 0.67, TJ dataset AUC = 0.74 v.s. 0.66).Conclusions: ROS status is associated with chemotherapy resistance. ROS score system might be a prognostic biomarker in predicting the survival benefit from ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Background: Inhibitors of immune checkpoints have shown little effect in clinical trials involving glioma patients. Here, we explored novel targets for use in future treatments. Previous studies showed the sialic acid-binding Ig-like lectin (Siglec) family to have a specific role in immunosuppression. We aimed to study the characteristics and immune function of Siglec family members. Methods: Transcriptome data from 1024 glioma samples and 1551 glioma single cells were used in our study. Clinical and molecular pathology information was also included. Statistical, bioinformatical methods, and single-cell sequencing analysis were applied to investigate the role of Siglec family members. Results: Siglecs-5, −7, −9, and −16 showed a significant correlation with immunosuppression in glioma. They are typically expressed in higher grade, IDH-wildtype, and mesenchymal subtype gliomas. Siglec-5, −7, and −9 had a similar immune function to TIM-3, while Siglec-16 was similar to PD-L1, suppressing tumor immunity via different mechanisms. Joint use of Siglec-inhibitors and immune checkpoint inhibitors could prolong the survival of glioma patients. Conclusion: Siglec-5, −7, −9, and −16 suppressed tumor immunity in different ways. Joint usage of inhibitors may be an effective means to improve the efficacy of glioma immunotherapy. [ABSTRACT FROM AUTHOR]

DNA methylation, histone modifications, and miRNAs affect ovarian cancer (OC) progression and therapy response. Identification of epigenetically downregulated miRNAs in drug-resistant OC cell lines with a possible role in drug resistance and/or drug-induced mesenchymal-like phenotype. MiRNA profiling was performed on parental and carboplatin-resistant OC cells, MES-OV and MES-OV CBP. RT-qPCR validation, epigenetic modulation and other CBP-resistant OC cell lines were used to select miRNAs of interest. The integration of miRNA-predicted target genes and differentially expressed genes (DEGs), pathway and functional analysis were used for forecasting their biological role. Data mining was performed to determine their possible prognostic and predictive values. MiRNA profiling revealed 48 downregulated miRNAs in OC cells whose drug sensitivity and metastatic potential were impacted by epigenetic modulators. Of the fourteen selected, nine were validated as changed, and seven of these restored their expression upon treatment with epigenetic inhibitors. Only three had similar expression patterns in other OC cell lines. MiRNA-mRNA integrative analysis resulted in 56 target DEGs. Pathway analysis revealed that these genes are involved in cell adhesion, migration, and invasion. The functional analysis confirmed the role of miR-103a–3p, miR-17–5p and miR-107 in cell invasion, while data mining showed their prognostic and predictive values. Only miR-103a–3p was epigenetically regulated at the constitutive level. High throughput miRNA and cDNA profiling coupled with pathway analysis and data mining delivered evidence for miRNAs which can be epigenetically regulated in drug-resistant, mesenchymal-like OC cells as possible markers to combat therapy-induced short overall survival and tumor metastatic potential. [Display omitted] • Microarray analysis identifies 77 differentially expressed miRNAs in drug resistant EOC cells. • Epigenetic modulators impact cells' drug response and metastatic capacity. • Downregulated miR-103a, 17 and 107 are shared feature of several resistant EOC cell lines and has a prognostic value. • MiRNA-mRNA integrative analysis reveals signaling pathways involved in metastasis. • Epigenetically regulated miR-103a is involved in metastasis but not drug response. [ABSTRACT FROM AUTHOR]

• We developed Non-Contrast CT radiomics fusion model, combining ML, to predict the 6-month long-term outcomes of AIS patients receiving conventional treatment. • The prediction fusion model combined radiomics and clinical features. • NCCT GrayLevelNonUniformity and Skewness features were the top radiomics predictors of AIS outcomes. • The clinical-radiomics fusion model achieved good performance for predicting the AIS outcome. • NCCT based radiomics method could be a reliable imaging biomarker for early clinical decision-making. Accurate prediction of outcomes for patients with acute ischemic stroke (AIS) is crucial for clinical decision-making. In this study, we developed prediction models based on non-contrast computed tomography (NCCT) radiomics and clinical features to predict the modified Rankin Scale (mRS) six months after hospital discharge. A two-center retrospective cohort of 240 AIS patients receiving conventional treatment was included. Radiomics features of the infarct area were extracted from baseline NCCT scans. We applied Kruskal-Wallis (KW) test and recursive feature elimination (RFE) to select features for developing clinical, radiomics, and fusion models (with clinical data and radiomics features), using support vector machine (SVM) algorithm. The prediction performance of the models was assessed by accuracy, sensitivity, specificity, F1 score, and receiver operating characteristic (ROC) curve. Shapley Additive exPlanations (SHAP) was applied to analyze the interpretability and predictor importance of the model. A total of 1454 texture features were extracted from the NCCT images. In the test cohort, the ROC analysis showed that the radiomics model and the fusion model showed AUCs of 0.705 and 0.857, which outperformed the clinical model (0.643), with the fusion model exhibiting the best performance. Additionally, the accuracy and sensitivity of the fusion model were also the best among the models (84.8% and 93.8%, respectively). The model based on NCCT radiomics and machine learning has high predictive efficiency for the prognosis of AIS patients receiving conventional treatment, which can be used to assist early personalized clinical therapy. [ABSTRACT FROM AUTHOR]

Objective: Circulating immune‐inflammatory cells have been increasingly recognized as robust prognostic biomarkers in cancer. Here, we sought to evaluate the prognostic values of preoperative peripheral platelet, neutrophil, lymphocyte quantitation in patients with primary oral squamous cell carcinoma (OSCC). Materials and methods: A total number of 309 patients with primary OSCC surgically treated at our institutions were retrospectively included. Detailed demographic, clinicopathological, laboratory, and follow‐up data were collected. The Kaplan–Meier analysis and Cox regression assay were performed to assess the prognostic values. A new prognostic risk score was developed and designed as PNL (platelet–neutrophil–lymphocyte) score based on combined preoperative platelets, neutrophils, and lymphocytes via calculating the regression coefficients of each type of cell by Cox regression analysis. Results: High platelet counts (≥266 × 109/L), neutrophil counts (≥2.8 × 109/L), PNL scores, and low lymphocyte counts (<1.4 × 109/L) significantly associated with reduced overall and disease‐free survival (Kaplan–Meier, p < 0.05, Log‐rank test). Univariate and multivariate regression analyses revealed that individual platelet, neutrophil, lymphocyte quantitation, and PNL score were independent prognostic predictors for patient survival. Moreover, receiver operating characteristics curve revealed superior prognostic utility of PNL score for OSCC. Conclusions: Our findings indicate that preoperative circulating platelets, neutrophils, lymphocytes, and PNL score serve as noninvasive, low‐cost, and powerful prognostic predictors for patients with OSCC. [ABSTRACT FROM AUTHOR]

Steroid receptor coactivator 1 (Src-1) and Twist1 are aberrantly upregulated in a variety of tumors and play an important role in tumor progression. However, the exact role of Src-1 and Twist1 in nasopharyngeal carcinoma (NPC) is uncertain. In this study, we investigated the possible prognostic value and biological effect of Src-1 and Twist1 in NPC. Src-1 and Twist1 expression was detected in a cohort of NPC patients (n = 134) by qRT-PCR. Kaplan-Meier survival analysis was used comparing overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional hazard regression model. Biologic effect of Src-1 and Twist1 in NPC cell lines was evaluated by western blot, colony formation assay, soft agar assay, scratch wound healing assay, transwell invasion assay and tumor xenografts growth. We have found that Src-1 and Twist1 were aberrantly upregulated in human NPC tissues, and associated with advanced tumor stage, distant metastasis and unfavorable prognosis. Knockdown of Src-1 or Twist1 in human NPC cell line CNE-1 suppressed colony formation, anchorage-independent growth, cell migration, invasion and tumor xenografts growth, while enforced expression of Src-1 or Twist1 in human NPC cell line HNE-2 promotes anchorage-independent growth, cell migration and invasion. In addition, Src-1 and Twist1 could suppress E-cadherin expression and increase Vimentin expression, thus suggested that Src-1 and Twist1 enhanced the malignant behaviors of NPC cells via inducing epithelial-mesenchymal transition (EMT). Our data indicated that Src-1 and Twist1 could be possible prognostic biomarkers and potential therapy targets for patients with NPC. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma is the most common type of lung cancers. Whole-genome sequencing studies disclosed the genomic landscape of lung adenocarcinomas. however, it remains unclear if the genetic alternations could guide prognosis prediction. Effective genetic markers and their based prediction models are also at a lack for prognosis evaluation.Methods: We obtained the somatic mutation data and clinical data for 371 lung adenocarcinoma cases from The Cancer Genome Atlas. The cases were classified into two prognostic groups (3-year survival), and a comparison was performed between the groups for the somatic mutation frequencies of genes, followed by development of computational models to discrete the different prognosis.Results: Genes were found with higher mutation rates in good (≥ 3-year survival) than in poor (< 3-year survival) prognosis group of lung adenocarcinoma patients. Genes participating in cell-cell adhesion and motility were significantly enriched in the top gene list with mutation rate difference between the good and poor prognosis group. Support Vector Machine models with the gene somatic mutation features could well predict prognosis, and the performance improved as feature size increased. An 85-gene model reached an average cross-validated accuracy of 81% and an Area Under the Curve (AUC) of 0.896 for the Receiver Operating Characteristic (ROC) curves. The model also exhibited good inter-stage prognosis prediction performance, with an average AUC of 0.846 for the ROC curves.Conclusion: The prognosis of lung adenocarcinomas is related with somatic gene mutations. The genetic markers could be used for prognosis prediction and furthermore provide guidance for personal medicine. [ABSTRACT FROM AUTHOR]

The function of runt-related transcription factor 3 (RUNX3) in oral cancer remains controversial. The present study aimed to determine the status of RUNX3 protein expression and its association with clinicopathological characteristics in tongue squamous cell carcinomas (SCC). The present study used three pairs of tongue SCC and non-cancerous tissues to assess RUNX3 protein expression by western blot analysis, and two tongue SCC cell lines to determine RUNX3 protein localization by immunofluorescence and immunocytochemistry. Tissue microarray immunohistochemistry was performed to detect the clinical relevance of RUNX3 in 79 patients with tongue SCC. The results demonstrated that RUNX3 protein expression was reduced in tongue SCC tissues compared with in paired non-cancerous tissues. Similarly, the expression of RUNX3 was low in SCC25 and Cal27 cells, and was predominantly localized to the cytoplasm. In the 79 patients with tongue SCC, RUNX3 protein expression was presented in different manners in carcinoma nests and tumor stroma. RUNX3 in carcinoma nests (nRUNX3) exhibited nuclear positive staining in 24/79 samples, cytoplasmic mislocalization in 41/79 samples and was undetectable in 14/79 samples. RUNX3 in stroma (sRUNX3) exhibited nuclear positive staining in 40/79 samples and nuclear negative staining in 39/79 samples. Negative nRUNX3 expression was significantly associated with lymph node metastasis (P=0.014), clinical stage (P=0.027), and overall and disease-free survival (P=0.008 and P=0.007, respectively). In addition, negative sRUNX3 expression was associated with lymph node metastasis (P=0.003) and clinical stage (P=0.003); however, not with overall survival. The findings of the present study preliminarily suggested that cytoplasmic mislocalization of RUNX3 protein may be a common event in tongue SCC, and that sRUNX3 protein expression may be a potential prognostic biomarker. [ABSTRACT FROM AUTHOR]

The incidence and clinical implications of autoimmune diseases (ADs) in patients with non-Hodgkin's lymphoma(NHL) remain unclear. The aim of this study was to examine the prevalence of ADs in NHL and define the clinical characteristics and prognosis of AD-associated NHL patients. Patients diagnosed with NHL in our institute between 1995 and 2017 were retrospectively reviewed to assess the incidence of ADs. Of 4880 patients with NHL, 140 (2.9%) presented with autoimmunity, with a total of 24 ADs. The most common AD was Sjögren syndrome, followed by autoimmune cytopenia, psoriasis, rheumatoid arthritis, etc. Psoriasis and rheumatoid arthritis were significantly associated with pre-existing ADs, whereas autoimmune cytopenia was significantly associated with secondary AD. Sjögren syndrome was significantly associated with B-cell lymphoma, and systemic vasculitis was significantly associated with T-cell lymphoma. Patients with AD-associated NHL had a high frequency of extranodal involvement(87%), with significant associations between specific extranodal sites of lymphoma and subtypes of ADs. Among patients with available data on pre-treatment peripheral blood Epstein-Barr virus (EBV) DNA(n = 68), elevated EBV-DNA load was observed in a variety of NHL subtypes, including 20% of marginal zone lymphoma and 14.3% of follicular lymphoma patients. In a matched-pair analysis, survival did not differ significantly between NHL patients with and without ADs. However, for NHL patients with pre-existing ADs, a prior history of systemic corticosteroids therapy was significantly associated with worse survival (HR = 7.33, P = 0.006). Taken together, our data suggest that a broad spectrum of ADs is associated with NHL, and AD-associated NHL has distinct features with regard to clinical manifestations and prognosis. [ABSTRACT FROM AUTHOR]

Background: Simultaneous detection of multiple molecular biomarkers is helpful in the prediction of treatment response and prognosis for colorectal cancer (CRC) patients.Methods: A 22-gene panel consisting of 103 hotspot regions was utilized in the formalin-fixed paraffin-embedded (FFPE) tissue samples of 207 CRC patients, using the next-generation sequencing (NGS)-based multiplex PCR technique. Those 22 genes included AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, KRAS, MAP2K1, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, STK11, and TP53.Results: Of the 207 patients, 193 had one or more variants, with 170, 20, and 3 having one, two, and three mutated genes, respectively. Of the total 414 variants identified in this study, 384, 25, and 5 were single-nucleotide variants, deletion, and insertion. The top four frequently mutated genes were TP53, KRAS, PIK3CA, and FBXW7. There was high consistency between the results of NGS-PCR technique and routine ARMS-PCR in KRAS and BRAF mutation detection. Univariate and multivariate analyses demonstrated that advanced TNM stage, elevated serum CEA, total variants number ≥ 2, AKT1 and PTEN mutation were independent predictors of shorter DFS; poor differentiation, advanced TNM stage, total variants number ≥ 2, BRAF, CTNNB1 and NRAS mutation were independent predictors of shorter OS.Conclusions: It is feasible to detect multiple gene mutations with a 22-gene panel in FFPE CRC specimens. TNM stage and total variants number ≥ 2 were independent predictors of DFS and OS. Detection of multiple gene mutations may provide additional prognostic information to TNM stage in CRC patients. [ABSTRACT FROM AUTHOR]

FAM64A, a marker of cell proliferation, has been investigated as a potential biomarker in several cancers. In the present study, we examined the value of FAM64A expression in the diagnosis and prognosis of pancreatic cancer through bioinformatics analysis of data obtained from The Cancer Genome Atlas (TCGA) database. The diagnostic value of FAM64A expression in pancreatic cancer tissue was deteremined through receiver operating characteristic (ROC) curve analysis, and based on the obtained cut-off value, patients were divided into two groups (high FAM64A expression and low FAM64A expression). Chi-square and Fisher exact tests were applied to identify associations between FAM64A expression and clinical features. Moreover, the effect of FAM64A expression in the survival of pancreatic cancer patients was observed by Kaplan-Meier and Cox analyses. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Our results showed that high FAM64A expression in pancreatic cancer was associated with survival status, overall survival (OS), and recurrence. The area under the ROC curve was 0.736, which indicated modest diagnostic value. Patients with higher FAM64A expression had significantly shorter OS and recurrence-free survival (RFS) times. Multivariate survival analysis demonstrated that high FAM64A expression was an independent risk factor for OS and RFS. GSEA identified mitotic spindles, myc targets, MTORC1 signaling, G2M checkpoint, E2F targets, DNA repair, glycolysis and unfolded protein response as differentially enriched with the high FAM64A expression phenotype. In conclusion, high FAM64A mRNA expression is an independent risk factor for poor prognosis in pancreatic cancer. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) and Castleman’s disease (CD) share similar clinical manifestations. When the histopathology coincides with the diagnosis of both IgG4-RD and CD, it is hard to depart the two disease entities utterly; here we call it IgG4-CD provisionally. In this study, we aim to review the clinical features of IgG4-CD. This study is based on a retrospective analysis of a prospectively acquired database. IgG4-CD was defined histopathologically in patients who fulfilled the diagnosis of both IgG4-RD and CD. Forty-five definite IgG4-RD and 16 multicentric CD (MCD) patients were recruited as controls. Clinical features including organ involvement, serum IgG4, IgG, IgE, ESR, CRP, and IL-6 levels were collected and analyzed. Fifteen patients (2.8%) out of 534 patients with IgG4-RD in China’s largest prospective IgG4-RD and Mimicry cohort fulfilled the definition of IgG4-CD. There were 14 males and 1 female, whose mean age was 47 ± 18 years old, and the median disease duration before diagnosis was 12 (1-132) months. Eight patients have allergic disease history. IgG4-CD patients had more lymph node involvement (100 vs 57.8%, P < 0.01), while IgG4-RD patients had more submandibular (33.3 vs 77.1%, P < 0.01) and parotid gland (13.3 vs 40.9%, P < 0.05) affected. IgG4-CD patients had significantly higher levels of ESR, CRP, IgG, IgG1, IgG3, IgG4, and IgE than IgG4-RD patients. Compared with MCD patients, IgG4-CD patients showed higher incidence of salivary gland and paranasal sinus involvement, higher hemoglobin, eosinophil count, serum IgG4 level and IgG4/IgG ratio, and lower CRP, IL-6 levels, and IgG1/IgG, IgG2/IgG ratio. All patients with IgG4-CD exhibited relatively favorable outcomes. Both IgG4-RD and CD can involve multiple organs. There are a small group of patients who had clinical and pathological characteristics of both CD and IgG4-RD showed better clinical outcome. In the long-term prognosis of these patients, the relationship of CD and IgG4-RD is waiting to be further elucidated. [ABSTRACT FROM AUTHOR]

Background: Reactive thymic hyperplasia (RTH) is seen in children and adolescents receiving chemotherapy for various malignancies. However, it is not clear why this occurs only in some patients. The aim of this study was to identify the predictors for RTH in children and adolescents receiving chemotherapy for lymphoma and to determine the effect of RTH on prognosis.Methods: We reviewed the medical records of 126 lymphoma patients (October 2007-October 2012). The patients were divided into two groups according to different criteria, i.e., age at initial diagnosis (2-12 years vs. 13-18 years); presence of thymic infiltration at baseline (yes vs. no); and receipt of mediastinal radiotherapy (yes vs. no). The Kaplan-Meier method and multivariate Cox regression model analysis were used to analyze predictors for RTH. Further, patients were divided into two groups according to the occurrence of RTH during follow-up, and Kaplan-Meier survival analysis was used to analyze the prognostic value of RTH.Results: The 2-12-year-old group had a shorter duration from the end of therapy to RTH than the 13-18-year-old group (median: 3 months vs. 16 months) and a higher rate of RTH (97.1% vs. 60.3%, P < 0.001). The lymphoma thymic non-infiltration group had a shorter duration from the end of therapy to RTH than the lymphoma infiltration group (median: 4 months vs. 22 months), and a higher rate of RTH (88.2% vs. 57.6%, P < 0.001). The non-mediastinal radiotherapy group had higher rate of RTH than the mediastinal radiotherapy group (84.7% vs. 12.5%, P < 0.001). Low age, absence of thymic infiltration by lymphoma at baseline, and absence of mediastinal radiation were predictors for RTH by multivariate Cox regression analysis (P < 0.05). The RTH group had a lower recurrence rate than the non-RTH group (13.9% vs. 40%), and a longer duration from the end of therapy to recurrence (median: 10 months vs. 5 months, P < 0.001).Conclusions: Younger age, absence of thymic infiltration by lymphoma at baseline and absence of mediastinal radiotherapy are predictors for RTH in children and adolescents. RTH may be a positive prognostic factor. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is one of the most common types of malignancy and is associated with high morbidity and mortality rates around the world. With poor clinical outcomes, potential biomarkers for diagnosis and prognosis are important to investigate.Objective: The aim of this study is to investigate the gene expression module of GC and to identify potential diagnostic and prognostic biomarkers.Method: Microarray data (GSE13911, GSE29272, GSE54129, and GSE79973), including 293 stomach tumor tissues and 196 normal tissues, were analyzed to identify differentially expressed genes (DEGs). DEGs were identified in four profiles by intersecting four overlapping subsets, including 90 downregulated and 45 upregulated DEGs in common. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses have been showed that extracellular matrix was the most enriched signal pathway. Furthermore, hub genes were analyzed by protein–protein interaction network and clinical outcomes were assessed by Kaplan–Meier survival analysis. Two independent datasets were used to validate the differential expression of two hub genes: Serpin Family E Member 1 (SERPINE1) and Secreted Protein Acidic and Cysteine Rich (SPARC).Results: Validation of independent datasets indicated that SERPINE1 and SPARC expression were drastically increased in gastric tumor tissues and associated with poor outcomes in GC patients. The expression of SERPINE1 was related to race (Asian and White) (P < 0.05).Conclusion: SERPINE1 and SPARC were significantly upregulated in gastric tissues and associated with poor outcomes. The investigations of SERPINE1 and SPARC may promote their predictive and prognostic value in GC. [ABSTRACT FROM AUTHOR]

DOK-1 and DOK-2 (DOK1/2) are closely related members of downstream of tyrosine kinase (DOK) family genes, which are found to be frequently rearranged in several hematopoietic cancers. However, the clinical implications of DOK1/2 in acute myeloid leukemia (AML) remain largely unknown. To investigate the clinical significance, real-time quantitative PCR (RQ-PCR)was carried out to detectDOK1/2 expressions in 125 de novo AML patients and 28 healthy controls. Real-time quantitative methylation-specific PCR (RQ-MSP) andbisulfite sequencingPCR(BSP)wereapplied todetectDOK1/2methylation level anddensity.DOK1/2expressionsweresignificantlydown-regulated inAMLpatients. The promoters of DOK1/2 were highly hypermethylated and negatively correlated with DOK1/2 expressions in AML patients. In addition, we also confirmed that DOK1/2 expressions could be restored by DOK1/2 demethylation using 5-aza-2′-deoxycytidine in leukemia cell line THP-1. Survival analyses showed that low-expressed DOK1/2 were associated withmarkedly shorter overall survival and leukemia free survival in both wholecohort AML and non-M3 AML patients. Multivariate analyses further revealed that DOK1/2 were act as independent prognostic factors in AML patients. These findings indicate that decreased DOK1/2 expressions associated with their promoter hypermethylations predict adverse prognosis in AML. [ABSTRACT FROM AUTHOR]

This work aims to study the roles and related mechanisms of six2 in 5-FU sensitivity of hepatocellular carcinoma (HCC) cells. KM-Plotter analysis showed that HCC patients with higher six2 expression levels had shorter overall survival. Six2 expression was higher in clinical HCC tissues than in normal tissues, and was negatively correlated with E-cadherin expression. Additionally, six2 overexpression decreased the sensitivity of HCC cells to 5-Fu, characterized as attenuating 5-FU-induced cell apoptosis and downregulation of cell viability, and promoted HCC cells stemness. Mechanistically, six2 overexpression repressed E-cadherin expression via stimulating promoter methylation of the E-cadherin. And E-cadherin overexpression rescued six2-induced decrease of 5-FU sensitivity and promotion on HCC cells stemness. Therefore, our results suggest that Six2 is negatively correlated with good prognosis and decreases 5-FU sensitivity via suppressing E-cadherin expression in HCC cells. [ABSTRACT FROM AUTHOR]

• Glycolytic genes combined with immune score could define differential prognoses of AML patients. • The Risk Score calculated by LASSO Cox model based on 6 genes (METTL7B, HTR7, ITGAX, TNNI2, SIX3 and PURG) can reliably predict the prognosis of AML patients. • Nomogram model based on Risk Score and other independent prognostic factors could also predict the prognosis and survival of AML patients. Acute myeloid leukemia (AML) is widely considered an immunoresponsive malignancy. However, potential association between glycolysis-immune related genes and AML patients' prognosis has been seldom studied. AML-related data was downloaded from TCGA and GEO databases. We grouped patients according to Glycolysis status, Immune Score and combination analysis, basing on which overlapped differentially expressed genes (DEGs) were identified. The Risk Score model was then established. The results showed that totally 142 overlapped genes were probably correlated with glycolysis-immunity in AML patients, among which 6 optimal genes were screened to construct Risk Score. High Risk Score was an independent poor prognostic factor for AML. In conclusion, we established a relatively reliable prognostic signature of AML based on glycolysis-immunity related genes, including METTL7B, HTR7, ITGAX, TNNI2, SIX3 and PURG. [ABSTRACT FROM AUTHOR]

CHFR acts as a tumor suppressor gene, which is frequently inactivated caused by its promoter hypermethylation in various solid tumors. Although a recent study showed that CHFR hypermethylation was a frequent event in acute myeloid leukemia (AML) and correlated with adverse clinical outcome, herein, we found that CHFR methylation was a rare event in patients with myeloid malignancies (including AML, chronic myeloid leukemia, and myelodysplastic syndromes), but its expression may serve as an independent prognostic biomarker in AML. CHFR expression was assessed by real‐time quantitative PCR, whereas CHFR methylation was detected by methylation‐specific PCR and bisulfite sequencing PCR. In AML patients, lower CHFR expression was associated with lower complete remission (CR) rate, and CHFR expression was significantly increased in CR after chemotherapy. Moreover, patients with lower CHFR expression showed shorter overall survival and leukemia‐free survival, and multivariate analysis confirmed that lower CHFR expression was an independent risk factor in AML. Importantly, the prognostic value of CHFR expression was validated using the published Gene Expression Omnibus datasets. Notably, CHFR promoter was nearly unmethylated in patients with myeloid malignancies. Our findings revealed that lower CHFR expression was independently associated with unfavorable prognosis in AML. Moreover, aberrant CHFR promoter methylation was a rare event in myeloid malignances. [ABSTRACT FROM AUTHOR]

Long non‑coding RNAs (lncRNAs) are primary regulators of cancer development via their involvement in almost every aspect of cell biology. Recent studies have indicated that lncRNAs serve pivotal roles in breast cancer (BC) progression; however, to the best of our knowledge, the role of the lncRNA BRAF‑regulated lncRNA 1 (BANCR) in BC has not yet been elucidated. The present study revealed that BANCR was overexpressed in BC cell lines and tissues, and could promote the clinical progression of disease, including increases in tumor size, lymph node metastasis and Tumor‑Node‑Metastasis stage. Furthermore, high BANCR expression was demonstrated to be associated with poor overall survival rates and early recurrence of BC in patients. Additionally, univariate and multivariate COX regression analyses identified high BANCR expression as an independent risk factor of poor prognosis of patients with BC. In addition, to verify the function of BANCR in BC cell lines, BANCR expression was silenced using short hairpin RNAs in MDA‑MB‑231 cells and overexpressed in MDA‑MB‑468 cells. An MTT assay and colony formation assay indicated that BANCR knockdown could suppress the proliferation of BC cells, whereas BANCR upregulation induced the proliferation of BC cells. Furthermore, BANCR silencing also reduced the migration and invasion of BC cells, as demonstrated via transwell migration and invasion assays. Consistently, the migration and invasion of BC cells increased upon BANCR ectopic overexpression in MDA‑MB‑468 cells. Mechanistically, matrix metallopeptidase 2/9 and epithelial‑mesenchymal transition markers may be the potential targets of BANCR in regulating BC metastasis. In conclusion, BANCR overexpression could promote the clinical progression, metastasis and proliferation of BC and indicate poor prognosis of patients with BC. BANCR may therefore be a potential prognostic marker and therapeutic target of patients with BC. [ABSTRACT FROM AUTHOR]

Abstract: The polarization of tumor‐associated macrophages (TAMs) and tumor‐associated neutrophils (TANs), especially from the antitumoral phenotype to the protumoral phenotype under certain conditions, has an important influence on the progression of tumors. However, the interactions and combined prognosis of these cells are poorly known. Here, we detected the infiltration of CD68+ TAMs, CD163+ TAMs, and CD66b+ TANs in the specimens from 662 patients with GC by immunohistochemistry. The results showed that the infiltration of each of CD163+, CD68+, and CD66b+ cells in GC tissue was significantly increased and independently associated with GC prognosis. Strong collinearity (r = 0.690, P < 0.001) was found between the infiltration of CD163+ and CD68+ cells in GC, and multivariate Cox analysis confirmed the infiltration of CD163+ cells was a better predictor for prognosis than that of CD68+ cells. The combination of the infiltration of CD163+ and CD66b+ cells provided more accurate survival prediction than any individual marker. Patient subgroups with CD66blowCD163low (hazard ratio (HR) = 2.161; 95% confidence interval (CI)  = 1.266–3.688; P < 0.001), CD66bhighCD163high (HR = 3.575; 95% CI = 2.155–5.933; P < 0.001), and CD66blowCD163high (HR = 7.514; 95% CI = 4.583–12.312; P < 0.001) were gradually associated with shorter DFS when compared with the subgroup with CD66bhighCD163low. The similar result was also for DSS among the subgroups. Moreover, the two‐marker model could more effectively discriminate the prognosis among the patients with chemotherapy than that among those without chemotherapy. We concluded that CD163+ TAMs were a more valuable prognostic marker than CD68+ TAMs, and CD163+ TAMs combined with CD66b+ TANs could more precisely predict the prognosis of patients with GC. [ABSTRACT FROM AUTHOR]

Background: WD repeat domain 5 (WDR5), a core member of Mixed lineage leukemia (MLL) and SET1 histone H3 lysine 4 (H3K4) methyltransferase complexes, is involved in multiple biological and pathological processes. Its deregulation in cancer and pro-tumorigenic roles has been increasingly appreciated. However, the expression pattern of WDR5 and its biological functions in head neck squamous cell carcinoma (HNSCC) have not been well established.Methods: The expression of WDR5 mRNA in HNSCC was determined by data mining and interrogation using publicly available databases. Its protein expression was measured by immunohistochemistry in a retrospective cohort of primary HNSCC samples. Moreover, the associations between WDR5 expression and various clinicopathological parameters and patient survival were assessed. The pro-tumorigenic roles of WDR5 in HNSCC were further delineated in vitro by loss-of-function assay.Results: Our bioinformatics analyses revealed that WDR5 mRNA was significantly overexpressed in 3 HNSCC cohorts. WDR5 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with large tumor size, advanced clinical stage (chi-square test, P = .048, .006) and reduced overall and disease-free survival (Kaplan-Mier analyses, Log-rank test, P = .0137, .0154). Univariate and multivariate survival analyses further revealed WDR5 protein abundance as an independent prognostic factor for patients' overall survival. Moreover, WDR5 knockdown significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis in HNSCC cells.Conclusions: Our findings reveal that WDR5 is aberrantly overexpressed in HNSCC and associates with aggressiveness and unfavorable prognosis, thus representing a novel diagnostic and prognostic biomarker for HNSCC. [ABSTRACT FROM AUTHOR]

Accumulating studies have shown that miR-216b acted as a tumor suppressor and was down-regulated in solid tumors. However, little studies revealed the role or clinical implication of miR-216b in blood cancers. Herein, we reported miR-216b expression and its clinical significance in patients with acute myeloid leukemia (AML). In the current study, we analyzed bone marrow (BM) miR-216b expression in 115 de novo AML patients examined by real-time quantitative PCR. Notably, BM miR-216b expression was significantly up-regulated in AML patients, and could serve as a potential biomarker distinguishing AML from controls. No significant correlations of BM miR-216 expression were found with sex, age, white blood cells, hemoglobin, platelets, BM blasts, French-American-British classifications, and karyotypes. Significantly, patients with high miR-216b expression tended to have a lower frequency of FLT3-ITD mutation and higher incidence of U2AF1 and IDH1/2 mutations. Moreover, complete remission (CR) rate and overall survival were negatively affected by BM miR-216b overexpression among cytogenetically normal AML (CN-AML). Cox regression analyses showed that highBM miR-216b expression may act as an independent risk factor in CN-AML patients. Among the follow-up patients, BM miR-216b level in CR phase was markedly lower than in diagnosis time, and was returned in relapse phase. Collectively, our findings indicated that miR-216b overexpression was a frequent event in de novo AML, and independently conferred a poor prognosis in CN-AML. Moreover, miR-216b expression was a valuable biomarker correlated with disease recurrence in AML. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes (TILs) are regarded as adaptive immune response of the host to cancer cells and valuable prognostic factors. Here, we sought to characterize the densities and locations of CD3+ and CD8+ TILs in primary oral squamous cell carcinoma (OSCC) samples and assess their clinicopathological and prognostic significance.Methods: A total number of 169 OSCC samples from 2 independent patient cohorts (Nanjing cohort, 93 cases; Wuxi cohort, 76 cases) were retrospectively collected. The numbers of CD3+ and CD8+ TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by immunohistochemistry and calculated. The optimal cutoff values for CD3+ and CD8+ TILs to stratify patients were determined by X-tile software in Nanjing cohort and further utilized in Wuxi cohort. The associations between CD3+ /CD8+ TILs and clinicopathological parameters or patient survival were assessed. The prognostic values of CD3+ / CD8+ TILs were evaluated by Cox regression analyses.Results: CD3+ and CD8+ TILs were identified at both CT and IM and enriched at IM. High density of CD3+ TILs at IM (CD3 IM) was significantly associated with increased overall and disease-specific survival (P < .05). High density of CD8+ TILs at CT (CD8 CT) was significantly associated with increased overall but not disease-specific survival. Moreover, CD3 IM and CD8 CT were identified as independent prognostic factors for patient survival.Conclusions: Our findings provide further evidence to support the prognostic values of CD3+ and CD8+ TILs for OSCC, suggesting that TIL subsets might be viable biomarkers and therapeutic targets with translational significance. [ABSTRACT FROM AUTHOR]

Background: Aberrant level of serum bilirubin, marker of hepatobiliary and hematological disorders, was associated with patient prognosis in several human malignancies. In this study, we aim to evaluate the predictive value of serum bilirubin for clinicopathologic characteristics and survival of patients with oral squamous cell carcinoma (OSCC).Methods: This study retrospectively reviewed 129 patients with OSCC and 129 normal controls matched for age and sex. The association between levels of preoperative direct bilirubin (DBIL), indirect bilirubin (IBIL), total bilirubin (TBIL), and clinical variables was analyzed. A proportional hazards regression model was used to find out the independent predictors of survival.Results: Significantly lower TBIL (P = .009) and IBIL (P < .001) were found in OSCC patients compared with normal controls. DBIL (P = .011) and lymph-node metastasis (P = .031) were found to be independent prognostic factors. Patients with higher DBIL (≥4.0 μmol/L) had longer overall survival than those with lower DBIL (P = .002). Patients with both lymph-node metastasis and lower DBIL showed the shortest overall survival (P = .001).Conclusions: Lower DBIL was associated with a poorer prognosis and may be regarded as an independent prognostic marker for patients with OSCC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to comprehensively summarize the epidemiological, clinicopathological characteristics, treatments as well as prognosis of Castleman’s disease (CD) identified in the oral maxillofacial and neck region.Materials and methods: Patients with CD in the oral maxillofacial and neck were retrieved from disease registry at our institution from Jan. 1990 to Dec. 2015. Systematic reviews from both English and Chinese literature were performed to collect the detailed information about the oral maxillofacial and neck CD. The epidemiological, clinicopathological data and treatment outcomes were further statistically analyzed.Results: Four patients with the oral maxillofacial and neck CD were identified and histologically confirmed as hyaline-vascular type. They underwent surgical excision without recurrence during the follow-up. Systematic literature reviews identified 221 cases from 123 eligible articles which satisfied the inclusion criteria. In 225 patients, most patients were diagnosed as unicentric (207) or hyaline-vascular type (205) of CD and identified in the neck, and treated by surgical resection with good prognosis. In contrast, the minority of patients was multicentric or plasma-cell/mixed type and treated by chemotherapy with inferior outcomes. Kaplan-Meir analyses revealed that both clinical and pathological types were significantly associated with patients’ overall survival.Conclusions: Although rare, most cases of the oral maxillofacial neck CD are found in adults and classified as unicentric and hyaline-vascular type of CD. Complete surgical excision is preferred with favorable prognosis for unicentric disease, whereas chemotherapy is usually exploited for multicentric disease with inferior outcomes.Clinical relevance: These data provide comprehensive information about the epidemiology, clinicopathological features, treatments, and outcomes of the oral maxillofacial and neck CD. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the relationship between intra-abdominal infection (IAI) and sarcopenia prospectively and to construct a nomogram to identify patients at a high risk of IAI.Methods: We conducted a prospective study of 682 consecutive patients with gastric cancer who underwent radical gastrectomy. The sarcopenia elements, including lumbar skeletal muscle index, handgrip strength, and gait speed, were measured before surgery. Factors contributing to IAI were determined through univariate and multivariate analysis. A nomogram consisting of the independent risk factors was constructed to quantify the individual risk of IAI.Results: Of the 682 patients enrolled in this study, 132 patients were diagnosed with sarcopenia and 61 were diagnosed with IAI. Logistic analysis revealed that sarcopenia, tumor size, pathological type, and multivisceral resection were independent prognostic factors for IAI. The nomogram model for IAI was able to reliably quantify the risk of IAI with a strong optimism-adjusted discrimination (concordance index, 0.736).Conclusions: Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and practical instrument to quantify the individual risk of IAI and could be used to identify patients at a high risk. [ABSTRACT FROM AUTHOR]

Activation of Wnt/β-catenin signaling played a crucial role in tumorigenesis, and β-catenin ( CTNNB1 ) overexpression has been identified in numerous solid tumors. The present study was designed to determine CTNNB1 expression and its clinical significance in Chinese de novo acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the pattern of CTNNB1 expression in 140 AML patients and 46 controls. The level of CTNNB1 transcript in AML patients was significantly up-regulated compared with controls ( P <  0.001). CTNNB1 high patients showed significantly older age than CTNNB1 low patients ( P <  0.05). The frequency of high CTNNB1 expression was significantly observed in patients with intermediate/poor karyotypes. CTNNB1 high patients had a significantly lower complete remission (CR) rate than CTNNB1 low patients ( P  = 0.004). Among cytogenetically normal AML (CN-AML), CTNNB1 high patients presented significantly shorter overall survival (OS, P  = 0.004) and leukemia-free survival (LFS, P  = 0.038) than CTNNB1 low patients. Multivariate analysis confirmed that CTNNB1 expression was an independent prognostic factor for OS among CN-AML. Moreover, CTNNB1 expression level significantly decreased after CR stage ( P  = 0.032) and increased in relapsed stage ( P  = 0.015). Our findings suggest that CTNNB1 is overexpressed and confers a poor prognosis in AML, and could be used as a biomarker in monitoring disease recurrence. [ABSTRACT FROM AUTHOR]

Summary: Aims: Despite therapeutic advances in glioma management including surgery, radiation, and chemotherapy, the improvement of patient outcome is far from satisfactory. Nucleolar and spindle‐associated protein 1 (NUSAP1) is an important functional protein during mitosis, and its abnormal expression is implicated in progression of different types of tumors. However, the role of NUSAP1 in gliomas remains unclear. Methods: NUSAP1 expression in gliomas with different grades was investigated based on GEO glioma datasets. Kaplan‐Meier survival analysis was used to evaluate its prognostic significance. In vitro assays were also performed to evaluate effects of NUSAP1 on malignant phenotypes of glioma cells by silencing NUSAP1. Results: NUSAP1 expression was correlated not only with glioma grade but also with prognosis of glioma patients. NUSAP1 depletion suppressed proliferation of U251 cells by inducing cell cycle arrest at G2/M phase and apoptosis. NUSAP1 depletion rendered U251 cells impaired migratory ability as well. Conclusion: NUSAP1 is a potential prognosis marker for glioma patients and therapeutic strategies targeting NUSAP1 might hold promise in improving glioma treatment. [ABSTRACT FROM AUTHOR]

Oncogenic role of miR-19 family has been identified in human cancers especially in lymphoid malignancies. However, to date, little studies investigated the role of miR-19 family in myeloid malignancies. Herein, we examined miR-19a/b expression and explored its clinical significance in de novo acute myeloid leukemia (AML). The detection of miR-19a/b expression was performed by real-time quantitative PCR in bone marrow mononuclear cells of 113 patients and 42 healthy donors. Both miR-19a / b levels were significantly increased in AML patients in contrast to controls. Patients with miR-19a/b overexpression were more frequently occurred in female, and had an older age. Moreover, cases with miR-19a overexpression had a higher frequency of U2AF1 , C-KIT and CEBPA mutations, whereas miR-19b overexpressed cases harbored U2AF1 and IDH1/2 mutations. There was no significant association of miR-19a overexpression with complete remission (CR) rate and overall survival (OS) among whole-cohort AML, non-M3 AML, and cytogenetically normal AML (CN-AML). However, although miR-19b overexpression was not correlated with CR rate, patients with miR-19b overexpression presented significantly shorter OS in whole-cohort AML and a trend in non-M3 AML and CN-AML patients. Importantly, our data also showed that miR-19a/b expression level at CR phase was lower than diagnosis time, and was returned to primary level even higher when at relapse phase. Our findings revealed that miR-19a/b overexpression were frequent events in de novo AML patients. Moreover, up-regulation of miR-19b expression was associated with poor prognosis and disease recurrence in AML. [ABSTRACT FROM AUTHOR]

Alveolar soft part sarcoma (ASPS) is a rare soft tissue neoplasm. The incidence of orbital involvement is the highest in ASPS arising in the head and neck region. However, limited information is available regarding its clinical characteristics. The present study presents the clinical manifestations, imaging findings, pathological features, treatment strategies and prognosis records of 8 cases of orbital ASPS over the last 15 years in a single hospital, along with a review of the literature. Included were 3 male and 5 female patients, with the median age at presentation being 9.5 years. The mean average largest tumour diameter was 3.6 cm. A total of 5 patients underwent surgical excision of the tumour, with 2 undergoing orbital exenteration and 1 undergoing partial orbital exenteration. In total, 6 patients received postoperative radiotherapy and 2 received chemotherapy. Upon follow-up, 6 patients were doing well with no evidence of recurrence or metastasis. Local recurrence developed in 2 patients, of whom 1 succumbed following withdrawal from treatment. According to the present series and the cases mentioned in the literature, orbital alveolar soft part sarcoma has characteristics distinct from those of alveolar soft part sarcoma which arises in other locations. Orbital alveolar soft part sarcoma presents itself in a younger population with a shorter course of disease, smaller tumour size, improved prognosis, a marked association with the extraocular muscles and with the Ki-67 proliferation index possibly associated with prognosis of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether the modified-nutrition index (m-NI) is a prognostic factor for the overall survival (OS) in nasopharyngeal carcinoma (NPC) patients who undergo intensity-modulated radiotherapy (IMRT). Methods: Clinical data were prospectively collected from NPC patients who underwent IMRT at our hospital between October 2008 and December 2014. The patient nutritional status before radiotherapy was evaluated using the m-NI, based on eight nutrition indicators including body mass index, arm muscle circumference, albumin, total lymphocyte count, red blood cell count, hemoglobin, serum pre-albumin, and transferrin. The independent prognostic value of m-NI for the OS was evaluated. Results: A total of 323 patients (229 males, 94 females) were included in this study, and the follow-up rate was 99.7% (322/323). The 1-, 3-, and 5-yr OS rates between malnutrition and normal nutrition groups by using the m-NI were 93.0% vs. 96.9%, 76.4% vs. 82.8%, and 61.8% vs. 77.1%, respectively. A regression analysis showed that the m-NI was the significant prognostic value for the OS in NPC. Conclusions: The m-NI before radiotherapy is a significant prognostic factor for the OS in NPC patients. Further validation of our instrument is needed in other NPC patients. [ABSTRACT FROM AUTHOR]

Recent studies suggest that several bacterial species are involved in tumor immunosurveillance and antitumor immunity. The role of bacteria in immune responses in HBV-related hepatocellular carcinoma (HCC) patients is still unknown. In this study, we examined the bacteria-reactive CD8 + T cell response in patients with HBV-related HCC. We found that circulating CD8 + T cells from healthy individuals demonstrated minimal or zero specificity toward a series of commensals and bacteria previously associated with antitumor effects, including Escherichia coli , Enterococcus faecium , Bifidobacterium longum , Bacteroides fragilis , and Enterococcus hirae . In contrast, the circulating CD8 + T cells from HBV-related HCC patients presented significantly elevated bacteria-reactive responses, albeit with high variations among different HCC individuals. Reactivity toward bacteria was also identified in tumor-infiltrating CD8 + T cells. These bacteria-reactive responses were not primarily induced by TLR ligand, but were dependent on the presence of antigen-presenting monocytes, and were MHC class I-restricted. Interestingly, we observed that the CD8 + T cell-to-Foxp3 + regulatory T cell ratio was positively correlated with the proportions of Bifidobacterium longum -reactive and Enterococcus hirae -reactive CD8 + T cells, while the frequency of PD-1 + CD8 + T cells was negatively correlated with the frequency of Enterococcus hirae -reactive CD8 + T cells. Furthermore, the disease-free survival time of HCC patients after tumor resection was positively correlated with the frequencies of Bifidobacterium longum -reactive and Enterococcus hirae -reactive CD8 + T cells. Together, these results suggested that certain bacterial species might present valuable antitumor effects. [ABSTRACT FROM AUTHOR]

Background Invasive fungal disease (IFD) is a major complication of acute leukemia, thus primary antifungal prophylaxis (PAP) is recommended by guidelines. Nevertheless, guidelines might not be commonly followed in developing countries due to economic factors. The primary objectives were to evaluate the implementation rate of PAP in acute leukemia patients in China and to compare the prognosis of IFD with and without PAP. The secondary objectives were to investigate the safety of PAP, clinical characteristics of IFDs and risk factors of breakthrough. Methods This was a retrospective observational single-center study, including non-M3 acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients receiving uniform induction or salvage chemotherapy between 2012 and 2016. Results There were 29.4% of patients without PAP among a total of 248 cases. The incidence of breakthrough proven/probable/possible IFDs was 24.7%, 6.5%, 5.5%, 5.4% and 5.3% in control (no prophylaxis), fluconazole, itraconazole, voriconazole and posaconazole group respectively ( P = 0.007), while the percentage of patients requiring empirical or pre-emptive therapy was 54.8%, 45.7%, 23.3%, 18.9%, 10.5% respectively ( P < 0.001). PAP could also significantly improve IFD-free survival ( P < 0.001) and reduce 90-day overall mortality in patients on AML salvage regimen ( P = 0.021). There were no statistical differences in PAP-related adverse events. Past history of IFD (OR 9.5, P = 0.006) was confirmed to be independent risk factors. Conclusions There are a considerable number of acute leukemia patients without PAP in China, who have higher IFD incidence, increased empiric/pre-emptive antifungal drug use and worse IFD-free survival. [ABSTRACT FROM AUTHOR]

Background: Undifferentiated connective tissue disease (UCTD) is widely considered to be a distinct clinical entity, and now divided into two subgroups: stable UCTD and early UCTD. The most frequent onset symptoms of UCTD include arthralgias, arthritis, Raynaud's phenomenon, mucocutaneous involvement, and sicca symptoms. However, Neurologic involvement is rare, and intracranial lesion as onset symptom in a patient with early UCTD has not yet been reported.Case Presentation: A 51-year-old Chinese female experienced progressive left leg weakness for 14 days before hospitalizing in our department. The lesion on right parietal lobe was initially detected by brain magnetic resonance imaging. Although the patient declined a cerebral biopsy, the possibility of stroke, cerebral venous sinus thrombosis, NMOSD, MS, autoimmune encephalitis, intracranial infections, and malignant tumors as cause of the lesion was excluded by intracranial angiogram, CSF study, MRI enhancement and MRS examination. Moreover, immunologic studies showed high titer of antinuclear antibody, increased erythrocyte sedimentation rate and C-reactive protein. These results led to a diagnosis of early UCTD with central nerve system (CNS) involvement. After low dose corticosteroid and azathioprine therapy, the patient's symptoms, abnormalities in immunologic tests and cerebral radiologic examinations were all greatly improved within a short duration.Conclusions: This is the first report of intracranial lesion as onset symptom in a patient with early UCTD. Our case suggested that central nerve system (CNS) involvement could be the onset symptom in early UCTD, and should be recognized quickly with exclusion of other causative factors in the differential diagnosis. Prompt and adequate treatment with low-dose steroid and immunosuppressive drugs could improve the prognosis of both early UCTD and CNS involvement. [ABSTRACT FROM AUTHOR]

A probabilistic framework is developed for the prognosis of battery packs. It is demonstrated using aging campaign data, that aging models alone may not be sufficient for aging prognosis, and aging model parameter estimation may further improve the accuracy of prognosis. A systematic framework that extends the aging models to battery pack aging and prognosis still remains challenging. We propose a framework that bridges the gap in cell and pack aging prognosis in a probabilistic sense, and further improves the prognosis by estimating the aging model parameters for the pack. The framework is versatile for various applications because it is not restricted to a specific cell chemistry, or a type of aging model. In addition, the proposed framework could distinguish more aged cells as compared to other cells in the pack. Numerical examples are provided to demonstrate the effectiveness of the proposed framework. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have shown Kinesin family member 20A (KIF20A) may play a critical role in the development and progression of cancer. However, the clinical value of KIF20A in nasopharyngeal carcinoma (NPC) is unknown. Here, we investigated the expression pattern of KIF20A in NPC and its correlation with clinicopathological features of patients. Methods: Real-time PCR and Western blotting were used to quantify KIF20A expression in NPC cell lines and clinical specimens compared with normal controls. KIF20A protein expression was also examined in archived paraffin embedded tumor samples from 105 patients with pathologically confirmed NPC by immunohistochemistry (IHC). Statistical analyses were applied to assess the associations between KIF20A expression and the clinicopathological features and survival outcomes. Effects on migration and invasion were assessed by wound healing and transwell invasion assays after KIF20A silencing. Results: KIF20A was significantly overexpressed at both the mRNA and protein levels in NPC cell lines and human tumor tissues. 45/105 (42.9%) of NPC specimens expressed high levels of KIF20A among the KIF20A detectable cases. Statistical analysis revealed that high KIF20A expression was significantly associated with gender (P = 0.046), clinical stage (P<0.001), T category (P = 0.022), N category (P<0.001), distant metastasis (P = 0.001) and vital status (P = 0.001). Moreover, Higher KIF20A expression patients had shorter overall survival (OS) and progression-free survival (PFS) (P = 0.001 and P = 0.001; log-rank test). In multivariate analysis, KIF20A was an independent prognostic factor for OS and PFS in the entire cohort (P = 0.033, P = 0.008). Knock down of KIF20A expression significantly suppressed NPC cell’s migration and invasion. Conclusions: KIF20A is overexpressed and may serve as an independent prognostic biomarker in NPC. Targeting KIF20A reduces migration and invasion of NPC cells. [ABSTRACT FROM AUTHOR]

A sort of PRCC with distinct eosinophilic cytoplasm named Oncocytic Papillary Renal Cell Carcinoma (OPRCC) has been increasingly attracting the attention of researchers recently. However, owing to the rarity of OPRCC, the clinicopathological and genetic features of the tumor have still not been well elucidated and whether it should be regarded as an independent subtype of PRCC remains controversial. Herein, a cohort of 14 OPRCCs was studied with the aim of revealing the distinct clinicopathological features, facilitating the classification and correct diagnosis of OPRCC. Men and women each accounted for a half of the cohort with the median age of 64 years old. The majority of patients (9/14) were identified by medical examination and the remaining presented with macroscopic haematuria or lumbar pain. Grossly, tumors were well demarcated and varied from 1.5 to 9 cm in diameter. Microscopically, typical OPRCC possessed fine papillary structures with delicate fibrovascular cores, lined with a single layer cell with large, deeply eosinophilic granular cytoplasm and round or polygonal-shaped nucleus exhibiting low nuclear grade in 10 cases (WHO/ISUP grade I-II). Most cases (12/14) possessed hemosiderin-laden and foam-like cells. Focal necrosis presented in 5 cases. Furthermore, solid oncocytoma-like areas appeared in 5 cases and focal sarcomatoid differentiation was identified in 1 case. Immunohistochemically, the majority of tumors presented high expression rates of alpha-methylacylCoA racemase (AMACR), CD10 and vimentin, which were similar to type 2 PRCC. The immune markers including cytokeratin-7 (CK7), KSP-cadherin and EMA exhibited variable positive immunostaining. Genetically, FISH analysis demonstrated trisomy of chromosome 7 in 7 OPRCCs and trisomy of chromosome 17 in 6 OPRCCs. Among 7 male cases, loss of chromosome Y was revealed in 2 cases. Follow-up data was available in 13 patients and only 1 patient died of bone metastasis of the tumor. The other 12 patients were all alive uneventfully at a mean follow-up time of 37 months, indicating that OPRCC is a unique subtype of PRCC with indolent clinical behavior. In conclusion, OPRCCs show a single layer tumor cell of low nuclear grade similar to type 1 PRCC, and abundant eosinophilic cytoplasm resembling type 2 PRCC. Furthermore, the tumor presents the same immunophynotype as type 2 PRCC but the same genetic features and prognosis as type 1 PRCC. OPRCC should be classified as an independent subtype of PRCC with different features from both type 1 and type 2 PRCC. [ABSTRACT FROM AUTHOR]

Background: Diabetes has been identified as an adverse prognostic variable which associated with an increased mortality in various cancers, including colorectal, lung, and breast cancers. However, previous studies provided inconsistent results on the association between diabetes and nasopharyngeal carcinoma (NPC). The main aim of this study was to investigate the associations between diabetes mellitus and the survival of NPC patients. Methods: This study was designed as a 1:2 matched case–control study. Cases were patients who met the criteria for the diagnosis of type 2 diabetic mellitus (DM) below. Controls, matched 1:2, were patients who were normoglycemic (NDM). The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model. Results: Both locoregional relapse-free survival (LRRFS) and disease-free survival (DFS) in the NDM group were higher than that in the DM group (p = 0.001 and p = 0.033). Additionally, subset analyses revealed that the differences in OS, LRRFS, and DFS were all significant between the two groups in the N0-N1 subset (p = 0.007, p =.000 and p = 0.002). The LRRFS was higher in the NDM group in the III-IV, T3-T4 and N0-N1 subsets (p = 0.004, p = 0.002 and p =.000). In T3-T4 subset, the NDM group experienced higher DFS than the DM group (p = 0.039). In multivariate analysis, T stage and N stage were found to be independent predictors for OS, DMFS and DFS; chemotherapy was a significant prognostic factor for DMFS and DFS, age for OS, and diabetes for LRRFS and DFS. Conclusions: Type 2 diabetic mellitus is associated with poorer prognosis among patients with NPC. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms of XPA gene have been studied in several cancers such as rs10817938, rs2808668. However, the role of XPA polymorphisms in patients with oral squamous cell carcinoma (OSCC) remains unclear. Thus, we analyzed the association of XPA polymorphisms with OSCC risk, clinicopathological characteristics and prognosis in the present study. TaqMan genotyping was used to evaluate the frequency of rs10817938, rs2808668 polymorphisms in OSCC patients. The prognostic significance of these polymorphisms was evaluated using Kaplan-Meier curves, Log-Rank analyses, and the Cox proportional hazard model. Luciferase reporter assay, RT-PCR and western blot were used to determine whether rs10817938 could influence transcription activity and XPA expression. The results showed that individuals carrying TC and CC genotypes had significantly greater risk of developing OSCC (OR = 1.42, 95% CI 1.04–1.93; OR = 2.75, 95% CI 1.32–5.71, respectively) when compared with wild-type TT genotype at rs10817938. OSCC patients with C allele at rs10817938 were more susceptible to lymph metastases, poor pathological differentiation and late TNM stage (OR = 1.67, 95% CI 1.17–2.37; OR = 1.64, 95% CI 1.18–2.28; OR = 1.54, 95% CI 1.11–2.14; respectively). A significant gene-environment interaction between smoking and CC genotype at rs10817938 was observed (COR = 3.60, 95% CI 1.20–10.9) and data also showed that OSCC patients with CC genotype and C allele had worse survival (p<0.001 for both). The T to C substitution at rs10817938 significantly decreased transcription activity of XPA gene, XPA mRNA and protein were also decreased in individuals with C allele at rs10817938. In addition, no significant association of rs2808668 polymorphism with OSCC risk, prognosis could be observed. In conclusion, the present study showed that XPA rs10817938 polymorphism is a functional SNP in vitro and in vivo and a biomarker for poor prognosis in OSCC patients. [ABSTRACT FROM AUTHOR]

Background and aims Alanine-glyoxylate aminotransferase 2 (AGXT2) polymorphisms have been extensively studied to be associated with many cardiovascular diseases, with the exception of chronic heart failure (CHF). The aim of this study was to determine whether the AGXT2 rs37369 (V140I) polymorphism is associated with risk for and prognosis of CHF in Chinese patients. Methods 1000 CHF patients and 1200 healthy controls were recruited and polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used to determine the genotypes of rs37369 polymorphism. Tube formation assay and transwell migration assay were performed to assess the effects of asymmetric dimethylarginine (ADMA) and to explore the significance of rs37369 polymorphism in the pathogenesis of CHF. 140 CHF patients underwent a median follow-up of 38.7 months by telephone. Results The rs37369 GG genotype was significantly over-represented in CHF patients compared to controls (18.9% vs 14.7%, p = 0.009) and was significantly associated with increased risk of CHF ( p = 0.030), especially in patients with hypertension ( p = 0.021). Besides, the rs37369 GG genotype marginally increased the risk for CHF in smokers. ADMA stimulated migration and inhibited tube formation of cultured human umbilical vein endothelial cells (HUVECs). Overexpression of AGXT2 with pcAGXT2-rs37369-A or G plasmid reversed ADMA-induced HUVECs migration and tube formation. AGXT2 rs37369-A showed increased ADMA degradation activity and marginally prolonged the lifetime of CHF patients. Conclusions ADMA might accelerate the progression of CHF possibly by inhibiting angiogenesis and promoting migration of HUVECs. AGXT2 rs37369 polymorphism is associated with increased risk for CHF, which may due to distinct disparities of alleles in ADMA degradation. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating immune cells (TIICs) play a critical role in breast cancer (BC) prognosis, but little is known regarding the efficacy of endocrine therapy in patients with ER-positive BC with diverse immunological phenotypes. To investigate whether TIICs affect survival after endocrine therapy in patients with different BC molecular subtypes, data were gathered from six studies totaling 1900 samples. CIBERSORTx was used to analyze the invasion of 22 immune cell subpopulations using a bulk gene expression profile. The relationships of immune-related metagenes and immune cell subsets with survival (distant metastasis-free survival, relapse-free survival, and overall survival) were studied using Cox regression models with cell proportions modeled in quartiles. The immune score and IGHG3 and LCK gene activity were linked to a better prognosis. Among the immune cells, monocytes, resting CD4+ memory T cells and plasma cells were correlated with prolonged survival, while neutrophils, Tregs, M0 macrophages, and M2 macrophages were associated with an unfavorable prognosis. Similar effects were reported for the luminal A subtype. In the luminal B subtype, γδ T cells and eosinophils were favorable prognostic factors. Covariate-adjusted multivariate Cox regression analysis revealed that high proportions of resting CD4+ memory T cells and resting dendritic cells were correlated with a good prognosis. Meanwhile, neutrophils were associated with an unfavorable prognosis. Understanding how monocytes and macrophages interact in the tumor microenvironment may be a promising study focus. Comprehensive research on the cellular immune response in tumors could help facilitate the development of new treatments. • Tumor-infiltrating immune cells are associated with survival after endocrine therapy in breast cancer patients. • CIBERSORTx was utilized to infer immune cell subsets using a bulk gene expression profile. • Active IGHG3 and LCK genes are prognostically favorable for endocrine therapy. • Highly infiltrative CD4+ T cells associated with better response to endocrine therapy. [ABSTRACT FROM AUTHOR]

Background: The long non-coding RNA H19 plays a crucial role in solid tumor initiation and progression. However, the potential role of H19 and its clinical significance in acute myeloid leukemia (AML) remain largely elusive. Methods: H19 expression was detected by qPCR, and clinical significance in AML patients was further analyzed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data for AML were used as validation cohorts. The roles of H19 in cell proliferation and apoptosis were determined by cell proliferation assay and flow cytometry analysis. Results: H19 expression was significantly increased in AML patients but not associated with embedded miR-675 expression. Moreover, H19 overexpression was not dependent on the methylation pattern in H19 differentially methylated region/imprinting control region. Strong association was observed between H19 overexpression and patients' characteristics including sex, higher white blood cells, older age, and intermediate karyotype, FLT3-ITD, and DNMT3A mutations. In addition, H19 overexpression correlated with lower complete remission (CR) rate and shorter overall survival, and further confirmed by multivariate analyses. Importantly, the prognostic effect of H19 expression was validated by TCGA and GEO data. In the follow-up of patients, H19 expression in CR phase was lower than diagnosis time and returned at relapse time. Loss-of-function experiments showed that H19 exhibited anti-proliferative and pro-apoptotic effects in leukemic cell HL60. Furthermore, H19 expression was positively correlated with potential downstream gene ID2 in AML. Conclusions: Our findings revealed that methylation-independent H19 was a prognostic and predictive biomarker in AML, and H19/ID2 played crucial roles in leukemogenesis with potential therapeutic target value. [ABSTRACT FROM AUTHOR]

• High PTGES3 expressed in Lung adenocarcinoma. • The over-expression of PTGES3 was related to the poor prognosis of overall survival in LUAD patients (HR = 1.643, 95% CI = 1.140–2.370, p = 0.008). • The expression level of PTGES3 was positively correlated with the infiltrating levels of Th2 cells. Immune-infiltration was positively relationship with overall survival in lung adenocarcinoma (LUAD). Nevertheless, the potential clinical value of PTGES3, especially in terms of prognosis and tumor immune-infiltration in LUAD had not been fully elucidated. Original data available from TCGA and GEO databases and integrated via R3.6.3. Kaplan-Meier and Cox regression methods were used to examine the effect of PTGES3 expression in overall survival, and nomogram was performed to illustrate the correlation between the PTGES3 expression and the risk of LUAD. The associate between PTGES3 and cancer immune characteristics were analyzed via the TISIDB databases. Western blot and RT-qPCR were used to analyze PTGES3 expression in the clinical lung adenocarcinoma tissue samples or non-small cell lung cancer cell lines. PTGES3 mRNA and protein expression were significantly elevated in LUAD compared with normal lung tissues. Up-regulated PTGES3 was significantly associated with pathologic stage and TM stage. Kaplan-Meier survival analysis and subgroup analysis showed that up-regulated PTGES3 was associated with a worse overall survival of LUAD (HR = 1.71 (1.27–2.31), p < 0.001). Multivariate Cox analysis showed that high PTGES3 expression was an independent factor affecting overall survival (HR = 1.64 (1.14–2.37), p < 0.001). GO and KEGG analysis revealed that the cell cycle, regulation of DNA replication, and regulation of innate immune response were enriched. A positive correlation between PTGES3 expression and immune infiltrating levels of Th2 cells was found. PTGES3 may play an important role in the cell cycle and as an independent predictive prognostic biomarker correlates with immune infiltrates in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Our previous research and extensive epidemiological studies reproducibly demonstrated that miR-502 potentially targeted the expression of H4K20 methyltransferase SET8 in a wide spectrum of cancer. Yet, the direct targeting of SET8 by miR-502 has not been definitively proven. The clinical significance of the miR-502/SET8 regulatory circuit is also not clear. Here, we conducted cell-based experiments and clinical studies in a cohort of 279 breast cancer samples. We provide evidence that SET8 is a direct target of miR-502. Treatment with miR-502 or downregulation of SET8 suppressed cell proliferation and cell cycle, and reduced cell migration, invasion and EMT. Clinical analyses showed the miR-502 expression was lower in tumor tissues than in adjacent non-tumor tissues and had a significant inverse correlation with that of SET8. Furthermore, high expression of SET8 was significantly associated with poor overall survival (OS) and disease free survival (DFS) of breast cancer. The low expression ratio of miR-502 to SET8 mRNA was also significantly associated with poor OS. Thus, the miR-502/SET8 regulatory circuit emerges as a key regulator of the pathobiology of cancer and a focal point for possible therapeutic intervention. [ABSTRACT FROM AUTHOR]