Prognostic value of epithelial-mesenchymal transition markers in clear cell renal cell carcinoma

• Published in: Aging (Albany, NY.) Vol. 12; no. 1; pp. 866 - 883
• Main Authors: Xu, Hua, Xu, Wen-Hao, Ren, Fei, Wang, Jun, Wang, Hong-Kai, Cao, Da-Long, Shi, Guo-Hai, Qu, Yuan-Yuan, Zhang, Hai-Liang, Ye, Ding-Wei
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 08.01.2020
• Subjects: Biomarkers, Tumor; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Computational Biology - methods; Databases, Genetic; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Male; Molecular Sequence Annotation; Neoplasm Grading; Neoplasm Staging; Prognosis; Reproducibility of Results; Research Paper; ROC Curve; Tumor Microenvironment - genetics; clear cell renal cell carcinoma; predictive model; tumor microenvironment; prognosis; epithelial-to-mesenchymal transition
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.102660

Epithelial-to-mesenchymal transition (EMT) is important in tumor invasiveness and metastasis. We aimed to determine prognostic value of six key EMT markers ( , , , , , ) in clear cell renal cell carcinoma (ccRCC). A total of 533 ccRCC patients with RNASeq data from The Cancer Genome Atlas (TCGA) cohort were included for analysis. Gene expression of these EMT markers was compared between tumor and normal tissues based on Oncomine database and TCGA cohort. Their correlations with progression-free survival (PFS) and overall survival (OS) were also examined in both TCGA cohort and FUSCC (Fudan University Shanghai Cancer Center) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors. Functional enrichment analyses were utilized to describe biologic function annotations and significantly involved hallmarks pathways of each gene. We found that Epithelial marker, expression was lower, while mesenchymal markers ( , , , ) expression was higher in ccRCC primary tumors. In the TCGA cohort, we found that patients with higher expression of , or lower expression of had worse prognosis. Further, in the FUSCC cohort, we confirmed the predictive ability of mesenchymal markers and epithelial marker expression in PFS and OS of ccRCC patients. After generating Cox regression models, EMT markers ( , , , and ) were independent prognostic factors of both PFS and OS in ccRCC patients. Our preliminary EMT prediction model can facilitate further screening of EMT biomarkers and cast a better understanding of EMT gene function in ccRCC.