Genome-wide Analysis of the Alternative Splicing Profiles Revealed Novel Prognostic Index for Kidney Renal Cell Clear Cell Carcinoma

Overview

Journal J Cancer

Specialty Oncology

Date 2020 Feb 13

PMID 32047561

Citations 3

Authors

Li Gao

Rong-Quan He

Zhi-Guang Huang

Yi-Wu Dang

Yong-Yao Gu

Hai-Biao Yan

Sheng-Hua Li

Gang Chen

Affiliations

Soon will be listed here.

Abstract

Alternative splicing (AS) is a major mechanism that greatly enhanced the diversity of proteome. Mounting evidence demonstrated that aberration of AS are important steps for the initiation and progression of human cancers. Here, we comprehensively investigated the association between whole landscape of AS profiles and the survival outcome of renal cell carcinoma (RCC) patients using RNA-seq data from TCGA SpliceSeq. Because of the limited number size of deaths in kidney chromophobe renal cell carcinoma (KICH) and papillary renal cell carcinoma (KIRP) TCGA cohorts, we only conducted survival analysis in kidney clear renal cell carcinoma (KIRC). We further constructed prognostic index (PI) based on prognosis-related AS events and built correlation network for splicing factors and prognosis-related AS events. According to the results, a total of 5351 AS events in 3522 genes were significantly correlated with the overall survival (OS) of kidney clear cell renal cell carcinoma (KIRC) patients. Seven of the PI models exhibited preferable prognosis-predicting capacity for KIRC with PI-ALL reaching the highest area under curve value of 0.875. The splicing regulatory network between splicing factors and prognosis-related AS events depicted a tangled web of relationships between them. One of the splicing factors: KHDRBS3 was validated by immunohistochemistry to be down-regulated in KIRC tissues. In conclusion, the powerful efficiency of risk stratification of PI models indicated the potential of AS signature as promising prognostic markers for KIRC and the splicing regulation network provided possible genetic mechanism of KIRC.

Citing Articles

Significance and Possible Biological Mechanism for Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.

Ji H, Li J, Zhang G, Huang Z, Cheng J, Li S World J Oncol. 2024; 15(4):662-674.

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ROCK2-RNA interaction map reveals multiple biological mechanisms underlying tumor progression in renal cell carcinoma.

Hong Z, Chen X, Wang L, Zhou X, He H, Zou G Hum Cell. 2023; 36(5):1790-1803.

PMID: 37418232 DOI: 10.1007/s13577-023-00947-x.

TF-RBP-AS Triplet Analysis Reveals the Mechanisms of Aberrant Alternative Splicing Events in Kidney Cancer: Implications for Their Possible Clinical Use as Prognostic and Therapeutic Biomarkers.

He M, Hu F Int J Mol Sci. 2021; 22(16).

PMID: 34445498 PMC: 8395830. DOI: 10.3390/ijms22168789.

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