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Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority of kidney cancer death worldwide, whose incidence and mortality are not promising. Identifying ideal biomarkers to construct a more accurate prognostic model than conventional clinical parameters is crucial.Methods: Raw count of RNA-sequencing data and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA). Tumor samples were divided into two sets. Differentially expressed genes (DEGs) were screened in the whole set and prognosis-related genes were identified from the training set. Their common genes were used in LASSO and best subset regression which were performed to identify the best prognostic 5 genes. The gene-based risk score was developed based on the Cox coefficient of the individual gene. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess its prognostic power. GSE29609 dataset from GEO (Gene Expression Omnibus) database was used to validate the signature. Univariate and multivariate Cox regression were performed to screen independent prognostic parameters to construct a nomogram. The predictive power of the nomogram was revealed by time-dependent ROC curves and the calibration plot and verified in the validation set. Finally, Functional enrichment analysis of DEGs and 5 novel genes were performed to suggest the potential biological pathways.Results: PADI1, ATP6V0D2, DPP6, C9orf135 and PLG were screened to be significantly related to the prognosis of ccRCC patients. The risk score effectively stratified the patients into high-risk group with poor overall survival (OS) based on survival analysis. AJCC-stage, age, recurrence and risk score were regarded as independent prognostic parameters by Cox regression analysis and were used to construct a nomogram. Time-dependent ROC curves showed the nomogram performed best in 1-, 3-and 5-year survival predictions compared with AJCC-stage and risk score in validation sets. The calibration plot showed good agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis suggested several enriched biological pathways related to cancer. Conclusions:In our study, we constructed a gene-based model integrating clinical prognostic parameters to predict prognosis of ccRCC well, which might provide a reliable prognosis assessment tool for clinician and aid treatment decision-making in the clinic. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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DJ-1 is frequently overexpressed in a large variety of solid tumors, but the DJ-1 expression in laryngeal squamous cell cancer and its clinical ⁄ prognostic significance is unclear. We aimed to evaluate DJ-1 protein expression in glottic squamous cell carcinoma (GSCC) and to correlate this with clinicopathological data including patient survival. The expression of DJ-1 in GSCCs (60) and adjacent normal tissue (44) was assessed by immunohistochemistry and western blot analysis. In addition, the role of DJ-1 was investigated in tumorigenesis by transfecting DJ1-specific siRNA into laryngeal squamous cell carcinoma (LSCC) Hep-2 cells. Our data showed that positive expression of DJ-1 was found in 85% of GSCCs. In univariate survival analysis of the GSCC cohorts, a highly significant association between DJ-1 expression with shortened patient overall survival (5-year survival rate 92.9% vs 66.6%; P = 0.001; log rank test) was demonstrated. In multivariate analyses, DJ-1, tumor grading, and pT status were significant prognostic parameters for shortened patient overall survival. Furthermore, siRNA targeting DJ-1 can effectively inhibit DJ-1 expression, resulting in enhanced apoptosis and less proliferation of Hep-2 cells. We concluded that DJ-1 overexpression might be a novel independent molecular marker for poor prognosis (shortened overall survival) of patients with GSCC. (Cancer Sci 2010; 101: 1320-1325 L aryngeal carcinoma accounts for approximately 2.4% of new malignancies worldwide every year, of which over 95% are of the squamous cell carcinoma.(1,2) Glottic squamous cell carcinoma (GSCC) is the most common type of laryngeal cancer. Patients with GSCC often display considerable variability in survival.(3) It is of general importance to predict the biology of the tumor and, thus, the course of the disease in the individual patient to ensure adequate therapy and patient surveillance. Conventional prognostic and predictive markers for GSCC are nodal status, tumor grade, tumor status, and tumor type.(3) Additionally, molecular markers are being sought and established to allow for a refined classification of prognosis, especially in patient subgroups whose outcome can only insufficiently be predicted by conventional parameters. These include, among others, activation of various oncogenes (Ras, (4,5) Myc,epidermal growth factor receptor,and cyclin D1 (8) ), and tumor suppressor gene inactivation (P53 and p16).(9,10) However, accurate and reliable biomarkers that serve for prognosis have yet to be identified.DJ-1 encodes a conserved protein belonging to the ThiJ ⁄ PfpI ⁄ DJ-1 superfamily.(11) The THEMATICS (theoretical microscopic titration curves) predicted eight DJ-1 family members and three different probable functional classes.(12) The exact molecular function of DJ-1 is still unclear although increasing evidence suggests that DJ-1 plays a role in cancer cell lines to protect against stress (13)(14)(15) and affects cell survival by modulating the phosphorylation status of protein kinase B (PKB) ⁄ Akt, (16)(17)(18)...

Integrin β (ITGB) superfamily members have been reported to play important roles in multiple biological functions in various cancers. However, the prognostic and oncologic values of ITGB superfamily members have not been systematically investigated in pancreatic cancer (PC). In this study, the mRNA expression and biological functions of ITGB superfamily members in PC were evaluated by bioinformatic analysis. Our results demonstrated that ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were significantly associated with advanced AJCC stage and histologic grade, and worse prognosis in PC. A prognostic signature based on ITGB1, ITGB4, ITGB5 and ITGB6 showed a reliable predictive performance. Furthermore, one CpGs (cg20545410) in promoter region of ITGB1, four (cg18709893, cg15700850, cg20667796 and cg18326022) of ITGB4, two (cg10977398 and cg03518058) of ITGB5 and one (cg23008083) of ITGB6 were negatively associated with their corresponding mRNA expression, and positively associated with prognosis in PC. We also identified TFAP2A as the potential transcription factor for ITGB4, SP1 for ITGB1 and ITGB6, and FHL2 for ITGB5 and ITGB6. ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were all significantly involved in focal adhesion signalling pathway. ITGB1 and ITGB5 overexpressions also associated with up‐regulation of TGF‐β and WNT signalling pathway, whereas ITGB4 and ITGB6 overexpressions associated with up‐regulation of Notch signalling pathway. Besides, ITGB1, ITGB5 and ITGB6 overexpressions significantly correlated with immunosuppression in PC. In summary, our study investigated the multilevel prognostic and biological values of ITGB superfamily members in PC.

Background: Obg-like ATPase 1 (OLA1) has been found to have a dual role in cancers. However, the relationship between OLA1 and hepatocellular carcinoma (HCC) remains unclear. Results: High expression of OLA1 in HCC was detected in public datasets and clinical samples, and correlated with poor prognosis. Downregulation of OLA1 significantly inhibited the proliferation, migration, invasion and tumorigenicity of HCC cells. Mechanistically, GSEA showed that OLA1 might promote tumor progression by regulating the cell cycle and apoptosis. In addition, OLA1 knockdown resulted in G0/G1 phase arrest and high levels of apoptosis. OLA1 could bind with P21 and upregulate CDK2 expression to promote HCC progression. Conclusions: Overall, these findings uncover a role for OLA1 in regulating the proliferation and apoptosis of HCC cells. Materials and methods: The Cancer Genome Atlas and Gene ExpressionOmnibus datasets were analyzed to identify gene expression. Immunohistochemistry staining, western blot and real-time polymerase chain reaction were performed to evaluate OLA1 expression in samples. Cell count Kit-8, wound-healing, transwell and flow cytometry assays were used to analyze HCC cell progression. Subcutaneous xenotransplantation models were used to investigate the role of OLA1 in vivo. Coimmunoprecipitation was used to analyze protein interactions.

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BackgroundDJ-1 can induce the tumor cell proliferation and invasion via down-regulating PTEN in many malignant tumors, and correlated to prognostic significance. However, the tumorigenesis role and clinical significance of DJ-1 in supraglottic squamous cell carcinoma (SSCC) is unclear. We aimed to evaluate the DJ-1 the relationship between DJ-1 and clinicopathological data including patient survival.MethodsThe expression of DJ-1 and PTEN in SSCCs (52) and adjacent non-cancerous tissues (42) was assessed by immunohistochemistry (IHC), and the relationship between DJ-1 and clinicopathological data was analyzed.ResultsDJ-1 was detected mainly in SSCCs (88.5%) and less frequently in adjacent non-cancerous tissues (21.0%). PTEN expression was detected in 46.2% of SSCCs and in 90.5% of adjacent non-cancerous tissues. DJ-1 expression was linked to nodal status (P = 0.009), a highly significant association of DJ-1 expression with shortened patient overall survival (5-year survival rate 88.0% versus 53.9%; P = 0.007; log rank test) was demonstrated.ConclusionsOur data suggested that DJ-1 over-expression was linked to nodal status, and might be an independent prognostic marker for patients with SSCC.