1. Mutant CDKN2A regulates P16/p14 expression by alternative splicing in renal cell carcinoma metastasis
- Author
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Siyi Chen, Xiaodong Teng, Maode Lai, Chong Lai, Xiao-Dong Wen, Qingrong Sun, Yingjian Hou, and Honghe Zhang
- Subjects
0301 basic medicine ,Mutant ,Gene mutation ,medicine.disease_cause ,Pathology and Forensic Medicine ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,CDKN2A ,Databases, Genetic ,medicine ,Humans ,Gene Regulatory Networks ,Genes, Tumor Suppressor ,Carcinoma, Renal Cell ,Cyclin-Dependent Kinase Inhibitor p16 ,Oncogene Proteins ,Mutation ,business.industry ,Alternative splicing ,EZH2 ,Cell Biology ,medicine.disease ,Kidney Neoplasms ,Gene Expression Regulation, Neoplastic ,Alternative Splicing ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,business - Abstract
Objective Metastatic renal cell carcinoma (mRCC) is the important factor for patient mortality, meanwhile gene mutation constantly changes cancer prognosis in tumor process. Exploring the driver mutation in mRCC process become more and more important. Materials and methods We obtained the 15 paired primary and metastatic mRCC samples and analyzed specific mutation genes in the metastatic foci (SMGs) by next generation sequencing. Moreover, we explored the Correlated networks, Pathway and Gene Ontology (GO) enrichment results, prediction analysis of AS sites and prognosis of survival. Results We identify EPCAM, TMEM127, EZH2, EXT1, CDKN2A, PRF1, AIP, CDK4, PRKARIA as SMGs and find that CDKN2A mutation sites affect the prognosis of mRCC by altering splicing elements. Based on the differential analysis for SMGs in KIRC, we found that EPCAM, PRF1 and EZH2 were differential expression in both primary tumors with metastasis compared to primary tumors without metastasis or metastatic tissues. By the AS prediction analysis, we suggest that CDKN2A mutation sites play an important role for RCC metastasis by affecting the p16/p14 expression. Conclusions The SMGs could provide new molecular cues associated with tumor metastasis and have potential clinical implications for cancer prognosis and treatment. Definitive conclusions await further validation and follow up.
- Published
- 2021
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