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Article type: Research Article
Authors: Cao, Huifenga | Cheng, Lianga | Yu, Junjuana | Zhang, Zhihuib | Luo, Zhenguoa | Chen, Dayina; *
Affiliations: [a] Department of Urology, First Affiliated Hospital of Jiamusi University, Jiamusi City, Heilongjiang, China | [b] Department of Urology, Hongqi Hospital Affiliated to Mudanjiang Medical College, Mudanjiang City, Heilongjiang, China
Correspondence: [*] Corresponding author: Dayin Chen, Department of Urology, First Affiliated Hospital of Jiamusi University, No. 348 Dexiang Street, Jiamusi City, Heilongjiang, 154000, China. Tel.: +86 454 8623540; Email: [email protected].
Abstract: OBJECTIVE: To identify the mRNAs associated with bladder cancer (BC) recurrence. METHODS: The transcription profile of GSE31684 including 39 recurrent BC tumor samples and 54 non-recurrent BC tumor samples as well as transcription profile of GSE13507 including 36 recurrent BC tumor samples and 67 non-recurrent BC tumor samples were downlaoded from the Gene Expression Omnibus. Then, the differentially expressed genes (DEGs) were identified using linear models for microarray data (limma) and the intersections of DEGs from the two datasets were further screened. The weighed gene co-expression network analysis (WGCNA) was used to screen the modules related to BC recurrence. Protein-protein interaction (PPI) network analysis was used to analyze the genes interaction. Their functions were predicted by Gene Ontology and KEGG pathway enrichment. Moreover, The Comparative Toxicogenomics Database 2017 update (CTD) was used to search the BC related pathway. The univariate cox regression analysis was used to identify DEGs associated to the recurrence. Kaplan-Meier plots were used to illustrate recurrence free survival time (RFS). RESULTS: A total of 692 intersections DEGs were screened. WGCNA showed that 7 modules (2279 genes) were stable in both the datasets. A total of 169 intersection DEGs were mapped to the 7 modules. There existed 149 interaction relationships among 81 proteins (18 down-regulated and 63 up-regulated DEGs) in the PPI network. Two KEGG pathways including Focal adhesion and ECM-receptor interaction were enriched which were also found in the CTD. The univariate cox regression analysis showed that 3 DEGs (COL4A1, COL1A2 and COL5A1) were significant related to the prognosis. Multivariate cox regression analysis revealed that pathologic_N (N0-N1 vs N2-N3, p= 0.033) were independent prognostic factors for overall survival in patients with BC. CONCLUSION: COL4A1, COL1A2 and COL5A1 could be associated with BC recurrence.
Keywords: Biomarker, bladder cancer, recurrence, mRNA, weighed gene co-expression network analysis
DOI: 10.3233/CBM-190617
Journal: Cancer Biomarkers, vol. 28, no. 4, pp. 429-437, 2020
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