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Ovarian cancer (OC) is characterised by heterogeneity that complicates the prediction of patient survival and treatment outcomes. Here, we conducted analyses to predict the prognosis of patients from the Genomic Data Commons database and validated the predictions by fivefold cross-validation and by using an independent dataset in the International Cancer Genome Consortium database. We analysed the somatic DNA mutation, mRNA expression, DNA methylation, and microRNA expression data of 1203 samples from 599 serous ovarian cancer (SOC) patients. We found that principal component transformation (PCT) improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than the decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes. Our study provides perspective on building reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC. What is already known on this subject? Recent studies have focussed on predicting cancer outcomes based on omics data. But the limitation is the performance of single-platform genomic analyses or the small numbers of genomic analyses. What do the results of this study add? We analysed multi-omics data, found that principal component transformation (PCT) significantly improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than did decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes. What are the implications of these findings for clinical practice and/or further research? Our study provides perspective on how to build reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC for future studies. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is closely correlated with malignant biological characteristics and poor survival. Recently, chemokines have been reported to be involved in the progression of tumors, and they can also regulate the tumor microenvironment. However, it is unclear whether chemokine-related long noncoding RNAs (lncRNAs) affect the prognosis of ESCC. Methods: We downloaded RNA-seq and clinical data from the Gene Expression Omnibus (GEO database. Chemokine-related lncRNAs were screened by differential analysis and Pearson correlation analysis. Then, prognosis-related lncRNAs were screened by using univariate COX regression, and risk models were constructed after the least absolute shrinkage and selection operator (LASSO) regression and multivariate COX regression. The predictive value of the signature was assessed using Kaplan–Meier test, time-dependent receiver operating characteristic (ROC) curves, decision curve analysis (DCA) and calibration curve. Moreover, a nomogram to predict patients' 1-year 3-year and 5-year prognosis was constructed. Gene set enrichment analyses (GSEA), Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG), evaluation of immune cell infiltration, and estimation of drug sensitivity were also conducted. Results: In this study, 677 chemokine-related lncRNAs were first obtained by differential analysis and Pearson correlation. Then, six chemokine-related lncRNAs were obtained by using univariate COX, LASSO and multivariate COX to construct a novel chemokine-related lncRNAs risk model. The signature manifested favorable predictive validity and accuracy both in the testing and training cohorts. The chemokine-related signature could classify ESCC patients into two risk groups well, which indicated that high-risk group exhibited poor prognostic outcome. In addition, this risk model played an important role in predicting signaling pathways, immune cell infiltration, stromal score, and drug sensitivity in ESCC patients. Conclusions: These findings elucidated the critical role of novel prognostic chemokine-related lncRNAs in prognosis, immune landscape, and drug therapy, thus throwing light on prognostic evaluation and therapeutic targets for ESCC patients. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is characterised by heterogeneity that complicates the prediction of patient survival and treatment outcomes. Here, we conducted analyses to predict the prognosis of patients from the Genomic Data Commons database and validated the predictions by fivefold cross-validation and by using an independent dataset in the International Cancer Genome Consortium database. We analysed the somatic DNA mutation, mRNA expression, DNA methylation, and microRNA expression data of 1203 samples from 599 serous ovarian cancer (SOC) patients. We found that principal component transformation (PCT) improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than the decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes. Our study provides perspective on building reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC. What is already known on this subject? Recent studies have focussed on predicting cancer outcomes based on omics data. But the limitation is the performance of single-platform genomic analyses or the small numbers of genomic analyses. What do the results of this study add? We analysed multi-omics data, found that principal component transformation (PCT) significantly improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than did decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes. What are the implications of these findings for clinical practice and/or further research? Our study provides perspective on how to build reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC for future studies. [ABSTRACT FROM AUTHOR]

Background: Encephalitis associated with antibodies against alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is an extremely rare type of antibody-mediated encephalitis. This research aims to investigate the clinical characteristics and prognosis of anti-AMPAR encephalitis.Methods: This retrospective study enrolled nine patients with anti-AMPAR encephalitis. Demographic information, clinical manifestations, laboratory and radiological findings, treatment and response were collected and analyzed. These patients were followed up with an average period of 72 weeks to gather prognostic information.Results: Nine patients (7 females and 2 males) were enrolled with a mean age at disease onset of 59 years old. Three clinical pictures, including limbic encephalitis (n = 7; 78%), pure amnesia (n = 1; 11%) and fulminant encephalitis (n = 1; 11%) were identified. New symptoms of dysphagia and deafness were identified in the clinical spectrum of anti-AMPAR encephalitis. All patients had positive blood AMPAR antibodies, and six of them (67%) had paired positive antibodies in cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) was abnormal in 75% of the patients with no specific patterns recognized. Six patients (67%) had tumors, including lung cancers and thymomas. After immunotherapy and oncotherapy, partial improvement of neurological symptoms was observed among all 6 patients with available records during their hospitalization. After a mean follow-up of 72 weeks, 3 patients had marked decrease of modified Rankin Scale (mRS) score, 1 patient had unchanged mRS score, 4 patients died and the other one was lost.Conclusions: Anti-AMPAR encephalitis mainly presents as limbic encephalitis, and is paraneoplastic in 67% of cases. Thus, intensive screening for tumors is recommended for all anti-AMPAR patients. Although patients showed a good short-term therapeutic response, the overall prognosis was not satisfactory. [ABSTRACT FROM AUTHOR]

BACKGROUND: Occludin/ELL domain containing 1 (OCEL1) is a novel discovered protein with its molecular functions remaining unknown and its role in lung cancer has not been directly explored. OBJECTIVES: This study focused on the role of OCEL1 in the progression and prognosis of non-small cell lung cancer (NSCLC). METHODS: A public database and tissue samples (80 NSCLC tissue samples and paired normal lung samples) were used to compare differences in OCEL1 expression and investigate its relationship with clinical characteristics and prognosis. RESULTS: Compared to adjacent normal lung tissue samples, OCEL1 expression was significantly down-regulated in tumor tissues. In addition, there was a negative correlation between OCEL1 and Ki67 expression levels. Low OCEL1 expression was significantly associated with lymph node metastasis, higher TNM stage, and poor prognosis. Importantly, multivariate analysis identified OCEL1 expression as an independent predictor for unfavorable NSCLC prognosis. CONCLUSIONS: These results indicated that OCEL1 protein may serve as a novel prognostic biomarker in NSCLC. [ABSTRACT FROM AUTHOR]

Objective: To study the correlation between the long noncoding RNA HOX transcript antisense RNA (HOTAIR) gene rs17720428 single nucleotide polymorphism (SNP) and gastric cancer risk and prognosis. Methods: A case–control study was designed to assess the correlation between the HOTAIR rs17720428 SNP and gastric cancer risk in the Chinese Han population. The genotype of the HOTAIR rs17720428 locus was analyzed in 245 patients with gastric cancer and 245 healthy control subjects by Sanger sequencing. Results: The gastric cancer risk in patients with a G allele at the HOTAIR rs17720428 locus was 1.59 times higher than that in patients with a T allele (95% confidence interval [CI]: 1.16–2.17, p < 0.01). This SNP of HOTAIR rs17720428 locus was associated with an increased risk for developing gastric cancer in males (male: adjusted odds ratio = 1.60, 95% CI = 1.02–2.52, p = 0.04). Patients with the GG genotype at the HOTAIR rs17720428 locus had the lowest overall survival (OS) (16.4 months), followed by those with the TG (19.3 months) and TT (24.2 months) genotypes. The differences in OS were statistically significant among the different genotypes (p = 0.003). Conclusion: The HOTAIR rs17720428 SNP is correlated with the risk and prognosis of gastric cancer in the Chinese Han population. The presence of a G allele at this locus increases the risk of gastric cancer among males. [ABSTRACT FROM AUTHOR]

We aimed to develop and validate a predictive model to evaluate in-hospital mortality risk in HIV/AIDS patients with PCP in China. 1001 HIV/AIDS patients with PCP admitted in the Beijing Ditan hospital from August 2009 to January 2018 were included in this study. Multivariate Cox proportional hazard model was used to identify independent risk factors of death, and a predictive model was devised based on risk factors. The overall in-hospital mortality was 17.3%. The patients were randomly assigned into derivation cohort (801cases) and validation cohort (200 cases) in 8:2 ratio, respectively, in which in derivation cohort we found that 7 predictors, including LDH >350U/L, HR>130 times/min, room air PaO2 <70mmHg, later admission to ICU, Anemia (HGB≤90g/L), CD4<50cells/ul, and development of a pneumothorax, were associated with poor prognosis in HIV/AIDS patients with PCP and were included in the predictive model. The model had excellent discrimination with AUC of 0.904 and 0.921 in derivation and validation cohort, respectively. The predicted scores were divided into two groups to assess the in-hospital mortality risk: low-risk group (0-11 points with mortality with 2.15-12.77%) and high-risk group (12-21 points with mortality with 38.78%-81.63%). The cumulative mortality rate also indicated significant difference between two groups with Kaplan-Meier curve (p<0.001). A predictive model to evaluate mortality in HIV/AIDS patients with PCP was constructed based on routine laboratory and clinical parameters, which may be a simple tool for physicians to assess the prognosis in HIV/AIDS patients with PCP in China. [ABSTRACT FROM AUTHOR]

Background Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a common mitochondrial syndrome. The aim of this study was to conduct a survival analysis based on the clinical features of a Chinese MELAS patient cohort. Methods This is a retrospective single-center study. The MELAS patients were followed up for 1–8 years (median 4 years). The disease severity was evaluated by the modified Rankin Scale (mRS). The survival analysis was performed using Kaplan-Meier analysis and Cox proportional hazards model. Results A total of 138 subjects were enrolled, and the median disease duration was 7 years [interquartile range (IQR) 4–11 years]. The stroke-like episodes were the most common initial symptoms (70.3%). Seventeen (17.3%) subjects lost to follow-up. Of the 121 subjects who successfully completed the follow-up, 28 subjects died (mortality rate 23.1%). An acute stroke-like episode and/or status epilepticus were the predominant causes of death (42.9%). Among the surviving patients (n = 93), 39.8% (37/93) required assistance in daily life (mRS scores 3–5). The mRS scores were inversely correlated with the age of onset ( r = − 0.28, P = 0.0022) but not with the disease duration ( r = 0.10, P = 0.2709). The survival rate declined mainly within 12 years after the disease onset. The stroke-like episode as the initial symptom was an independent risk factor for death (hazard ratio = 2.86, 95% CI 1.03–7.94, P = 0.043). Conclusions MELAS had high mortality and morbidity in this cohort of Chinese patients. The early onset of stroke-like episodes might indicate the more severe form of the disease, highlighting the importance of management of stroke-like episodes to improve the prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the relationships between the clinicopathologic features and the expression of GCS in bladder cancer. Methods and materials: Using immunohistochemistry and Western blotting method, 75 bladder cancer specimens were tested for expression of GCS. The correlation of GCS with clinicopathologic features of the patients was analyzed in combination with clinical data. Statistics analyses were done with SPSS 13.0 software, χ2 test, Fisher''s exact test, Kaplan-Meier method, Log-rank test. Results: High and low level expression of GCS explored by immunohistochemistry were 61.3 (46/75) and 39.6 (29/75), respectively. The high expression group (n = 46) showed a significant correlation with high histologic grade (P = 0.021) and tended to show (P = 0.045) that up-expression of GCS was positive related to BNs with lymph node metastasis among the various clinicopathologic characteristics. The overall 5-year survival and disease-free survival rates were 39.5% and 18.4%, respectively. Mean overall survival time was 60.3 months for the low expression group and 45.1 months for the high expression group. Mean disease-free survival was 36.2 months for the low-expression group and 27.3 months for the high-expression group. Conclusion: Our study suggested that up-regulation of GCS might make an aggressive choice of surgical therapy. A high expression of GCS seemed to be an indicator of poor prognosis. [Copyright &y& Elsevier]

Background: Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear. Methods: The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan–Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored. Results: In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers. Conclusions: In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response. [ABSTRACT FROM AUTHOR]

• The EMILIN2 expression was negatively correlated to the EMILIN2 methylation. • High expression of EMILIN2 predicted a poor prognosis in different databases. • EMILIN2 could be an independent prognostic biomarker in LGG. • EMILIN2 was enriched in many immune-related pathway. • EMILIN2 expression showed a correlation with gene makers in some immune cells. Low-grade gliomas (LGGs) are slow-growing brain cancer in central nervous system neoplasms. EMILIN2 is an extracellular matrix (ECM) protein which could influence the progress of some tumour which is unclear in LGG. In our study, the methylation, expression, prognosis and immune value of EMILIN2 in LGG were analysed through bioinformatics analysis. We analysed the LGG data from The Cancer Genome Atlas (TCGA) and discovered that the EMILIN2 expression, negatively correlated to the EMILIN2 methylation, could predict a poor prognosis and was associated with different clinical parameters. Moreover, univariate and multivariate Cox regression were performed in CGGA, which showed that the EMILIN2 could be an independent prognostic biomarker in LGG. Moreover, EMILIN2 expression showed a correlation with gene makers in some immune cells, which identified the significance of EMILIN2 in immune infiltration. Finally, we used RT-PCR to verify the EMILIN2 expression level in different grades which showed there were significantly different (P < 0.05). Similarly, high expression of EMILIN2 could predict a poor prognosis (P = 0.0078). In conclusion, EMILIN2 could act as an independent prognostic biomarker which might be associated with the malignancy and development of gliomas and play a crucial role in glioma in immune infiltration. [ABSTRACT FROM AUTHOR]

Background: The histone deacetylase (HDAC) family plays a significant role in a variety of biological processes related to cancer, such as metabolism and cancer progression, and recognized as a target of anti-cancer drugs. Nevertheless, there has been limited systematic research available regarding HDAC family in human cancers using multi-omics approaches. Objective: To evaluate the prognostic implications and immunological features of the HDAC family across multiple cancer types through comprehensive multi-omics analysis. Methods: We studied the associations of HDAC activity and a variety of factors, encompassing immune checkpoint genes, the tumor microenvironment (TME), instability of microsatellites (MSI), inherited mutations, variation in copy number, tumor mutation burden (TMB), and sensitivity to drugs in a variety of cancer types. Moreover, we analyzed the link between the degree of HDAC activity and the effectiveness of immunotherapy in several cohorts, providing significant details about the possible impact of HDACs on immunotherapeutic responses. Furthermore, we explored potential signaling pathways of HDACs in bladder cancer (BC) using gene set enrichment analysis (GSEA). Immune infiltration analysis in bladder cancer was performed based on HDACs expression, copy number or somatic mutations. Furthermore, the Human Protein Atlas (HPA) dataset has been used to validate the expression of the HDACs protein in BC. Results: The HDACs expression exhibits significant heterogeneity across different cancer types and is significantly correlated with patient prognosis, clinical traits, mutations, TME, TMB, MSI, immune checkpoint genes, and objective responses in immunotherapy. The drug sensitivity of cancers was found to be correlated with the gene expression of specific HDAC familial members. In BC, GSEA demonstrates enrichment of multiple immune-related functions and pathways; moreover, there are significant associations between genomic variations in HDACs and the degree of typical immunological cell recruitment. Furthermore, findings from differential expression analysis in BC are validated by protein expression analysis obtained from the HPA database. Conclusions: These findings reveal the significance of HDAC family in survival prognosis and treatment guidance of human cancers, and some of them have the potential to be used as immunotherapy biomarkers. [ABSTRACT FROM AUTHOR]

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) still present a huge threaten to women's health, especially the local advanced patients. Hence, developing more effectiveness prognostic signatures is urgently needed. This study constructed and verified a robust RNA-binding proteins (RBPs) related signature through a series of bioinformatics methods and explored the biological function of hub RBP in vitro experiments. As a result, the 10 RBPs signature was successfully established and could act as an independent prognostic biomarker in CESC patients, which displayed the highest sensitivity and specificity in prognosis prediction compared with other clinicopathological parameters. The risk model also presented good performance in risk stratification among CESC patients. Besides, a nomogram was constructed based on pathological stage and the risk signature and exhibited satisfactory accuracy in prognosis prediction. Functional enrichment indicated that the risk signature mainly participated in immune-related pathways and cancer-related pathways, and the infiltration level of immune cells and immune checkpoints showed a significantly higher degree in low-risk patients compared with high-risk patients. Notably, the 10 RBPs signature act as a novel biomarker in immunotherapy and chemotherapy response. In addition, PRPF40B was selected as hub RBP and its transcription and translation levels were obviously increased in CESC tissues, as well as Hela and Siha cells. Knockdown of PRPF40B inhibits the proliferation, migration and invasion of Hela and Siha cells in vitro. In conclusion, our research provides a noticeable strategy in prognostic prediction among CESC patients, which may illuminate the prospect of CESC patients' clinical outcome. [ABSTRACT FROM AUTHOR]

Background: The role of CIA‐II has been clarified in several types of tumors; however, whether dysregulated CIA‐II expression is also involved in the pathophysiology of lower‐grade glioma (LGG) remains undisclosed. Methods: A comprehensive pan‐cancer analysis of the expression patterns and prognostic significance of CIA‐II in miscellaneous tumors was undertaken. Subsequently, a detailed bioinformatics analysis was executed to identify putative correlations between CIA‐II expression and clinical features, prognosis, biological functions, immunological characteristics, genomic alterations, and chemotherapeutics in LGG. In vitro studies were implemented to examine the potential roles of CIA‐II in LGG. Results: CIA‐II expression was found to be abnormally elevated in a variety of tumors, including LGG. Additionally, patients with LGG with higher CIA‐II expression owned worse prognosis. Importantly, the results declared that CIA‐II expression was an independent prognostic indicator for LGG. Moreover, the expression of CIA‐II was tightly interrelated with immune cell infiltration, gene mutations, and chemotherapeutics in LGG. In vitro studies revealed that CIA‐II was increased and strongly related to the cell proliferation in LGG. Conclusion: CIA‐II may be an independent prognostic factor and a serviceable therapeutic target in LGG. [ABSTRACT FROM AUTHOR]

Glucose metabolism and DNA methylation play important roles in cancers. We aimed to identify glucose metabolism-related genes that were DNA methylation associated to establish a prognostic signature of bladder cancer (BLCA). With BLCA sample transcriptome data from The Cancer Genome Atlas (TCGA) and methylation data from TCGA 450 K microarray, glucose metabolism-related genes associated to prognosis and DNA methylation were identified and a prognostic signature was established. GSEA and WGCNA analysis were performed and two genes, UCHL1 and PYCR1, were selected for functional validations. 18 target genes were identified and the signature based on them was considered an effective and independent prognostic factor. Several pathways were enriched in the high-risk group by GSEA and three modules of genes were identified by WGCNA. UCHL1 and PYCR1 proliferated proliferation, migration and invasion ability of bladder cancer cells. The 18-gene signature is an independent prognostic factor for bladder cancer patients. • Glucose metabolism-related genes have potential to categorize bladder cancer subtypes. • 18 glucose metabolism-related, DNA methylation-related and survival-related genes are identified. • A signature based on the 18 target genes can serve as an independent prognostic factor for bladder cancer patients. • UCHL1 and PYCR1 promote bladder cancer cells' growth, migration and invasion. [ABSTRACT FROM AUTHOR]

Early recanalization after endovascular treatment could improve the prognosis of acute ischemia stroke. Futile recanalization often occurred which was one of the main causes of failure. By now the mechanisms of futile recanalization were not clear. They are probably concerned with bad collateral circulation, subacute reocclusion, large hypoperfusion volumes, microvascular compromise, and impaired cerebral autoregulation. Previous research found that some of the image markers could be used as the accurate predictors for poor prognosis after successful treatment in order to identify the patients who were not suitable for recanalization and reduce some of the unnecessary cost. Predictors for futile recanalization mentioned in our article can be used for supplement to make decision for endovascular treatment. [ABSTRACT FROM AUTHOR]

Recent studies have emphasized the close relationship between macrophages and tumor immunity, and the prognosis of lung adenocarcinoma (LUAD) patients is intimately linked to this. Nonetheless, the prognostic signature and classification of different immune patterns in LUAD patients based on the macrophages is largely unexplored. Two sc-RNAseq datasets of LUAD patients were collected and reprocessed. The differentially expressed genes (DEGs) related to macrophages between LUAD tissues and normal lung tissues were then identified. Based upon the above genes, three distinct immune patterns in the TCGA-LUAD cohort were identified. The ssGSEA and CIBERSORT were applied for immune profiling and characterization of different subtypes. A four-gene prognostic signature for LUAD patients was established based on the DEGs between the subtypes using stepwise multi-Cox regression. TCGA-LUAD cohort was used as training set. Five GEO-LUAD datasets and an independent cohort containing 112 LUAD samples were used for validation. TIDE (tumor immune dysfunction and exclusion) and drug sensitivity analyses were also performed. Macrophage-related differentially expressed genes were found out using the publicly available scRNA-seq data of LUAD. Three different immune patterns which were proved to have distinct immune infiltration characteristics in the TCGA-LUAD cohort were recognized based on the above macrophage-related genes. Thereafter, 174 DEGs among the above three different immune patterns were figured out; on the basis of this, a four-gene prognostic signature was constructed. This signature distinguished the prognosis of LUAD patients well in various GSE datasets as well as our independent cohort. Further analyses revealed that patients which had a higher risk score also accompanied with a lower immune infiltration level and a worse response to several immunotherapy biomarkers. This study highlighted that macrophage were significantly associated with TME diversity and complexity. The four-gene prognostic signature could be used for predicting outcomes and immune landscapes for patients with LUAD. [Display omitted] • Depicting the LUAD landscape and acquiring macrophage-related differentially expressed genes from scRNAseq data of LUAD. • Identifying and depicting 3 distinct LUAD subtypes with distinct immune landscapes which were termed as "immune-infiltrated phenotype", "immune-excluded phenotype" and "immune-desert phenotype". • Establishment of a four-gene prognostic model for LUAD patients and validation of the signature using publicly attainable LUAD cohorts and an independent cohort containing 112 LUAD samples. [ABSTRACT FROM AUTHOR]

Background: Coronavirus 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has created a tremendous economic and medical burden. The prevalence and prognostic value of SARS-CoV-2-induced kidney impairment remain controversial. The current study aimed to provide additional evidence on the incidence of acute kidney injury (AKI) in COVID-19 patients and propose the use of urinalysis as a tool for screening kidney impairment. Methods: 178 patients with confirmed COVID-19 were enrolled in this retrospective cohort study. The laboratory examinations included routine blood tests, blood biochemical analyses (liver function, renal function, lipids, and glucose), blood coagulation index, lymphocyte subset and cytokine analysis, urine routine test, C-reactive protein, erythrocyte sedimentation, and serum ferritin. Results: No patient exhibited a rise in serum creatinine or Cystatin C and occurrence of AKI, and only 2.8% of patients were recorded with an elevated level of blood urea nitrogen among all cases. On the contrary, 54.2% of patients who underwent routine urine testing presented with an abnormal urinalysis as featured by proteinuria, hematuria, and leucocyturia. Conclusions: Kidney impairment is prevalent among COVID-19 patients, with an abnormal urinalysis as a clinical manifestation, implying that a routine urine test is a stronger indication of prospective kidney complication than a blood biochemistry test. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of renal malignancy. Methyltransferase like 13 (METTL13) functions as an oncogene in most of human cancers, but its function and mechanism in ccRCC remains unreported.Methods: qRT-PCR, western blotting and immunohistochemistry were used to detect METTL13's expression in tissues. The effects of METTL13 on ccRCC cells' growth and metastasis were determined by both functional experiments and animal experiments. Weighted gene co-expression network analysis (WGCNA) was performed to annotate METTL13's functions and co-immunoprecipitation (co-IP) was used to determine the interaction between METTL13 and c-Myc.Results: METTL13 was underexpressed in ccRCC tissues compared to normal kidney tissues and its low expression predicted poor prognosis for ccRCC patients. The in vitro studies showed that knockdown and overexpression of METTL13 respectively led to increase and decrease in ccRCC cells' proliferation, viability, migratory ability and invasiveness as well as epithelial-mesenchymal transition (EMT). The in vivo experiment demonstrated the inhibitory effect that METTL13 had on ccRCC cells' growth and metastasis. Bioinformatic analyses showed various biological functions and pathways METTL13 was involved in. In ccRCC cells, we observed that METTL13 could negatively regulate PI3K/AKT/mTOR/HIF-1α pathway and that it combined to c-Myc and inhibited c-Myc protein expression.Conclusions: In general, our finding suggests that high expression of METTL13 is associated with favorable prognosis of ccRCC patients. Meanwhile, METTL13 can inhibit growth and metastasis of ccRCC cells with participation in multiple potential molecular mechanisms. Therefore, we suggest METTL13 can be a new diagnostic and therapeutic target for ccRCC in the future. [ABSTRACT FROM AUTHOR]

Introduction& Objectives: To evaluate the expression and methylation levels of histone deacetylase 9 (HDAC9) in clear cell renal cell carcinoma (ccRCC), investigate the correlations between the prognosis of ccRCC patients and HDAC9, and examine the associations between immunological parameters and HDAC9.Materials& Methods: The differences between HDAC9 expression in ccRCC tissues and normal tissues were evaluated with reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blotting and immunohistochemistry. HDAC9 methylation levels in ccRCC tissues and normal tissues were evaluated via The Cancer Genome Atlas and University of California, Santa Cruz Xena. Kaplan-Meier curves were also obtained from University of California, Santa Cruz Xena. Then, cell proliferation was examined via colony formation assays and 5-ethynyl-2'-deoxyuridine assays, and cell metastasis was investigated via transwell assays. Gene set enrichment analysis was conducted to examine the biofunctions of HDAC9. The relationships between HDAC9 expression and immunological parameters were assessed via the Tumor Immune Estimation Resource database.Results: HDAC9 down-regulation and hypomethylation were observed in ccRCC tissues and led to poor prognosis. HDAC9 up-regulation inhibited the proliferation and metastasis of ccRCC cells. A subset of the pathways identified by gene set enrichment analysis were associated with the immune response and inflammation, which were significantly positively correlated with HDAC9 expression in ccRCC. We confirmed that HDAC9 significantly promoted immune cell infiltration but was positively correlated with the expression of immune checkpoint molecules.Conclusion: Decreased expression and hypomethylation of HDAC9 lead to poor prognosis and inhibit immune cell infiltration in ccRCC. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Studies on MCI progression are important for Alzheimer's disease (AD) prevention. 18F fluoro-deoxy-glucose positron emission tomography (FDG-PET) has been proven to be a powerful tool for measuring cerebral glucose metabolism. In this study, we proposed a classification framework for MCI prediction with both baseline and multiple follow-up FDG-PET scans as well as cognitive scores of 33 progressive MCI (pMCI) patients and 46 stable MCI (sMCI) patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI).Method: First, PET images were normalized using the Yakushev normalization procedure and registered to the Brainnetome Atlas (BNA). The average metabolic intensities of brain regions were defined as static features. Dynamic features were the intensity variation between baseline and the other three time points and change ratios with the intensity obtained at baseline considered as reference. Mini-mental State Examination (MMSE) scores and Alzheimer's disease Assessment Scale-Cognitive section (ADAS-cog) scores of each time point were collected as cognitive features. And F-score was applied for feature selection. Finally, support vector machine (SVM) with radial basis function (RBF) kernel was used for the three above features.Results: Dynamic features showed the best classification performance in accuracy of 88.61% than static features (accuracy of 78.48%). And the combination of cognitive features and dynamic features improved the classification performance in specificity of 95.65% and Area Under Curve (AUC) of 0.9308.Conclusion: Our results reported that dynamic features are more representative in longitudinal research for MCI prediction work. And dynamic features and cognitive scores complementarily enhance the classification performance in specificity and AUC. These findings may predict the disease course and clinical changes in individuals with mild cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was performed to explore the impact of minimal residual disease (MRD) prior to transplantation on the prognosis for patients with acute lymphoblastic leukemia (ALL).Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted for relevant studies from database inception to March 2016. A total of 21 studies were included.Results: Patients with positive MRD prior to allogeneic stem cell transplantation (allo-SCT) had a significantly higher rate of relapse compared with those with negative MRD (HR = 3.26; P <  0.05). Pre-transplantation positive MRD was a significant negative predictor of relapse-free survival (RFS) (HR = 2.53; P <  0.05), event-free survival (EFS) (HR = 4.77; P < 0.05), and overall survival (OS) (HR = 1.98; P < 0.05). However, positive MRD prior to transplantation was not associated with a higher rate of nonrelapse mortality.Conclusions: Positive MRD before allo-SCT was a predictor of poor prognosis after transplantation in ALL.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: This study was carried out to investigate the prognostic value of baseline and dynamic changes in anxious emotion in advanced cancer patients undergoing palliative care.Methods: The association between anxious emotion and survival was investigated in a retrospective sample of 377 consecutive advanced cancer patients receiving palliative care from August 2013 to October 2015 and in an extended follow-up study of 106 of those patients.Results: The prevalence of anxious emotion was 24.93% (94/377) overall, 22.48% (47/209) in men and 27.97% (47/168) in women. Significant associations between baseline anxious emotion and overall survival (OS) were not found in the whole sample or in women. However, univariate and multivariate analyses showed that anxious emotion was an independent prognostic indicator of OS in men (hazard ratio [HR]: 1.811, P = .003). Moreover, findings showed that newly developed anxious emotion was significantly associated with poor OS in all readmitted patients (HR: 5.568, P < .001), in men (HR: 5.104, P = .006) and women (HR: 5.820, P = .004).Conclusions: Our study suggests that anxious emotion, especially dynamic changes in anxious emotion, needs to be monitored in advanced cancer patients; whether targeted interventions would prolong survival requires further studies. [ABSTRACT FROM AUTHOR]

Background: The lymphocytes played an important role in the natural history of cancer. The aim of this study was to explore the prognostic value of lymphocyte count and percentage for survival in advanced cancer patients receiving palliative care.Methods: A retrospective review of clinicopathological data from 378 consecutive advanced cancer patients and 106 extended follow-up patients treated with palliative care was conducted. Kaplan-Meier curves and multivariate cox regression analyses were used to evaluate the relationships of peripheral lymphocyte count (LC) and lymphocyte to white blood cell ratio (LWR) with overall survival (OS).Results: The median values for pretreatment LC and LWR were 1.1 (IQR, 0.8 ~ 1.5 × 109/L) and 0.138 (IQR, 0.086 ~ 0.208). The median survival times across LWR quartiles were 19, 47, 79, and 101 days (P < 0.001). Multivariate analysis indicated that patients in the highest quartiles of LC and LWR had an HR of 1.082 (95% CI 0.777 ~ 1.506, P = 0.642) and 0.466 (95% CI 0.328 ~ 0.661, P < 0.001), respectively, compared with patients in the lowest quartiles. Furthermore, only the dynamic changes of LWR were confirmed as an independent prognostic factor for overall survival during the follow-up (HR = 0.396, 95% CI 0.243 ~ 0.668; P = 0.001), as were primary tumor site and ECOG. No effect was observed for the dynamic changes of LC.Conclusions: Our findings demonstrate that measurement of the dynamic changes of LWR prior to treatment and during follow-up may represent a simple and new powerful prognostic factor for patients with advanced cancer, unlike measurement of LC. As a bedside marker of immune status, the prognostic role of LWR should be further evaluated in prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic value and clinicopathological significance of CD44 in ovarian cancer (OC) remain unclear. This meta-analysis, therefore, aims to evaluate the correlation between CD44 expression and OC.Methods: Studies published until March 2016 were searched in PubMed, EMBASE, and ISI Web of Knowledge databases. The odds ratio (OR) and the hazard ratio (HR) with 95 % confidence interval (CI) were used to assess the effects.Results: Twenty-four studies that include 2267 OC patients were identified for the final analysis. Sixteen studies investigated the expression difference of CD44 standard (CD44s) in 1848 patients. Results showed that high CD44s expression is associated with chemoresistance (OR 5.94, 95 % CI 1.91-18.47) and short disease-free survival (DFS) time (HR 2.57, 95 % CI 1.34-4.91). In addition, CD44s expression is not associated with tumor differentiation grade, residual mass, lymphoid nodal metastasis, and overall survival (OS). Ten studies investigated the expression difference of CD44v6 in 724 patients. Results showed that the CD44v6 expression is not correlated with FIGO stage, tumor differentiation grade, lymphoid nodal metastasis, and OS.Conclusion: High CD44s expression possibly indicates poor prognosis in OC patients given that high CD44s expression initiates chemotherapy resistance, although this expression pattern is not an independent predictive factor for OS. Meanwhile, high CD44s expression may be related to poor DFS of OC, but this relationship must be further confirmed. In addition, the result in which CD44v6 is not associated with OS of OC patients should be interpreted with caution. [ABSTRACT FROM AUTHOR]

The sodium channel epithelial 1 subunit gamma (SCNN1G) is mainly responsible for sodium entry and absorption. The dysfunction of SCNN1G has been widely studied in kidney-related diseases and chronic heart failure. However, its role in cancer remains unclear. Here, we found that SCNN1G was aberrantly downregulated in head and neck squamous cell cancer (HNSCC) tissues, which showed an efficifent diagnostic value according to the ROC curve analysis. The lower expression of SCNN1G was significantly correlated with lymphatic metastasis and a worse outcome of HNSCC patients. Ectopic overexpressing SCNN1G inhibited the invasive and migratory abilities of HNSCC cells, while knocking down SCNN1G showed an opposite effect. A positive correlation between SCNN1G and CDH1 expression was observed, which suggested that SCNN1G might impede HNSCC metastasis via strengthing cell-cell adherin. In addition, RAS signaling and ion channel transport signaling were enriched by SCNN1G in HNSCC using GSEA analysis, indicating that these signaling pathways might be the underlying mechanisms for SCNN1G as well. In addition, six sorts of immune infiltrate subtype cells were associated with SCNN1G expression. Our findings support that SCNN1G inactivation contributes to the metastasis of HNSCC. SCNN1G could serves as a valuable diagnostic and prognostic marker for HNSCC. [ABSTRACT FROM AUTHOR]

Background: High risk head and neck mucosal premalignancy has a malignant conversion rate of up to 40%, despite adequate surgical therapy. Epidermal Growth Factor Receptor (EGFR) blocking agents, including cetuximab, have shown activity in head and neck squamous cell carcinoma (HNSCC) and have potential for therapy in high risk premalignancy.Methods: We conducted a randomized, prospective, phase II clinical trial to determine the effects of cetuximab on patients with high risk premalignancy. Patients were randomized to treatment with cetuximab 400mg/m(2) on week one followed by 250mg/m(2) on week 2-8 or observation, with the option for crossover to cetuximab therapy for patients originally randomized to the observation arm.Results: Two of 19 enrolled patients did not complete therapy due to treatment toxicity. Analysis of 17 patients who completed the trial regimen show a trend toward a larger mean decrease in grade of dysplasia in the cetuximab treated group (-1.0) vs. the observation group (-0.2) (P=0.082, one-sided exact Wilcoxon rank sum test). However, in the observation group, none of the 5 patients (0%) achieved complete resolution of dysplasia; while 4 of 12 (33.3%) cetuximab treated patients had no remaining dysplasia after therapy.Conclusions: Treatment of high risk premalignancy of the upper aerodigestive tract with cetuximab alone may result in significant, durable, and complete clinical and histological resolution of moderate to severe dysplasia in at least a subset of high risk patients. These results warrant further investigation in larger studies with increased statistical power. [ABSTRACT FROM AUTHOR]

BACKGROUND Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited. METHODS A retrospective analysis of patients with recurrent OPSCC from 2 institutions between 2000 and 2012 was performed. p16 immunohistochemistry and/or in situ hybridization, as clinically available, were used to determine HPV tumor status. Clinical characteristics, distribution of recurrence site, and treatment modalities were compared by HPV tumor status. Overall survival (OS) was examined using Kaplan-Meier and Cox proportional hazards methods. RESULTS The current study included 108 patients with 65 locoregional and 43 distant metastatic first recurrences. The majority of patients were HPV-positive (80 patients). HPV-positive tumor status was associated with longer time to disease recurrence ( P<.01). Anatomic site distribution of disease recurrences did not differ by HPV tumor status. HPV-positive tumor status (adjusted HR [aHR], 0.23; 95% confidence interval [95% CI], 0.09-0.58 [ P = .002]), longer time to disease recurrence (≥1 year; aHR, 0.36; 95% CI, 0.18-0.74 [ P = .006]), and surgical salvage (aHR, 0.26; 95% CI, 0.12-0.61 [ P = .002]) were found to be independently associated with OS after disease recurrence. Surgical salvage was independently associated with improved OS compared with nonsurgical treatment among patients with both locoregional (aHR, 0.15; 95% CI, 0.04-0.56 [ P = .005]) and distant (aHR, 0.19; 95% CI, 0.05-0.75 [ P = .018]) metastatic disease recurrences. CONCLUSIONS Surgical salvage was found to be associated with improved OS for patients with recurrent locoregional and distant metastatic OPSCC, independent of HPV tumor status. Further prospective data are needed to confirm the role of surgical salvage for distant metastases. Cancer 2015;121:1977-1984. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND A subset of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV-OSCC) experience poor clinical outcomes. The authors of this report explored prognostic risk factors for overall survival (OS) and recurrence-free survival (RFS). METHODS Patients with incident HPV-OSCC who received treatment at the Johns Hopkins Hospital between 1997 and 2008 and who had tissue available for HPV testing as well as demographic and clinicopathologic information (N = 176) were included. Tissue was tested for HPV by in situ hybridization (ISH) and/or p16 immunohistochemistry. Demographic and clinicopathologic information was extracted from medical records. RESULTS In total, 157 of 176 patients (90%) with OSCC had HPV-associated disease (HPV-OSCC). In the patients with HPV-OSCC, the 3-year and 5-year OS rates were 93% (95% confidence interval [CI], 88%-98%) and 89% (95% CI, 81%-97%), respectively. Shorter survival was observed among older patients (hazard ratio [HR], 2.33 per 10-year increase; 95% CI, 1.05-5.16 per 10-year increase; P = .038), patients with advanced clinical T classification (HR, 5.78; 95% CI, 1.60-20.8; P = .007), and patients who were currently using tobacco (HR, 4.38; 95% CI, 1.07-18.0; P = .04). Disease recurrence was associated with advanced clinical T-classification (HR, 8.32; 95% CI, 3.06-23; P < .0001), current/former alcohol use (HR, 13; 95% CI, 1.33-120; P = .03), and unmarried status (HR, 3.28; 95% CI, 1.20-9.00; P = .02). Patients who remained recurrence free for 5 years had an 8.6% chance of recurrence by 10 years (1-sided 95% CI upper bound, 19%; P = .088). CONCLUSIONS In this study, prognostic risk factors were identified for patients with HPV-OSCC. The observed recurrence rates between 5 years and 10 years after definitive therapy need to be validated in additional studies to determine whether extended cancer surveillance is warranted in this cancer population. Cancer 2013;119:3462-3471.. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Collagen (COL) genes participate in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways, which play a crucial role in tumor invasion and metastasis. The prognostic value of COL genes has been shown for several malignancies. In the present study, we analyzed multiple microarray datasets using the Oncomine database to identify alterations of COL genes in gastric cancer (GC). Gene expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) in GC tissues and matched adjacent tissues. The prognostic value of differentially expressed COL genes in GC was evaluated by Kaplan-Meier survival analysis based on the complete mRNA transcriptomics data from The Cancer Genome Atlas (TCGA). We found that seven COL genes (COL1A2, COL4A1, COL4A2, COL6A1, COL6A2, COL6A3, and COL11A1) were elevated in GC. Among them, stepwise multivariate Cox regression was applied, and it was determined that COL4A1 and COL4A2 were signature and independent prognostic biomarkers in GC patients with obviously different overall survival (OS). High expression of COL4A1, COL4A2, COL6A1, COL6A2, and COL6A3 was correlated with poorer prognosis of GC patients treated by surgery only, while higher expression of COL4A1 and COL11A1 correlated with poorer survival of patients treated by 5-fluorouracil-based adjuvant therapy. Our results indicate that overexpression of COL genes might be utilized as novel prognostic markers for GC and assist with therapy selection. [ABSTRACT FROM AUTHOR]

• We established a long non-coding RNA signature to improve prognostic prediction in clear cell renal cell carcinoma. • LINC00488 and HOTTIP exhibited effects in promoting proliferation and inhibiting apoptosis in ccRCC cell lines. • LINC-PINT exhibited effects in inhibiting proliferation and promoting apoptosis in ccRCC cell lines. Accumulating research reports have indicated that long non-coding RNAs (lncRNAs) are abnormally expressed in many types of cancers. However, few lncRNA signatures for predicting cancer prognosis have been established. Our goal is to establish a lncRNA signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC). We downloaded KIRC lncRNA FPKM (Fragments Per Kilobase of transcript per Million Fragments) standardized expression data from The Cancer Genome Atlas (TCGA) by using the TANRIC tool. We established an 11-lncRNA signature that was clearly linked to the overall survival (OS) rates in the training and test sets. The training set was divided into the high-risk and low-risk subgroups, between which the OS was disparate (HR = 1.51, 95%CI = 1.39–1.64, P < 0.0001). The accuracy of the 11-lncRNA signature for predicting prognosis was confirmed in the test set. Further analysis revealed that the prognostic value of this signature was independent of the neoplasm grade and TNM stage. Gene set enrichment analysis (GSEA) was performed, and a summary of 4 gene sets related to canonical pathway, biological process, molecular function and cellular component was obtained. We demonstrated the biological function of these lncRNAs in ccRCC cell lines and found that LINC00488 and HOTTIP promoted tumour proliferation and inhibited apoptosis. However, LINC-PINT had the opposite effect. The establishment of the 11-lncRNA signature indicated the underlying biochemical functional roles of the selected lncRNAs in ccRCC. Our results may provide a reliable theoretical basis for clinical evaluation of ccRCC prognosis. [ABSTRACT FROM AUTHOR]