Abstract

Alternative splicing is an important modification process for the genome to generate mature mRNA by transcription, which has been found associated with survival in some tumors. However, systematic analysis of AS events in pan-renal cell carcinoma at the genome-wide level has been seldom conducted yet. In the current study, Upset plot and Venn plot were utilized to present the distribution characteristics of AS events. Those SREs were screened out with multivariate COX regression analyses, and functional enrichment analysis was performed to figure out potential pathways. ROC model was conducted to compare the efficiency of those potential SREs. A total of 2,169, 1,671, and 1,414 SREs were found in renal clear cell carcinoma (KIRC), renal chromophobe cell carcinoma (KICH), and renal papillary cell carcinoma (KIRP), respectively. Functional enrichment analysis results suggested possible mechanism such as changes in the branched-chain amino acid catabolic process due to SREs might play a key role in KIRC. The binary logistic regression equation based on the SREs had a good performance in each model compared to the single factor. The 5 year survival model presented that the AUC of the predicted probabilities in KIRC, KICH, and KIRP were 0.754, 1 and 0.841, and in the diagnostic model were 0.988, 0.970, and 0.999, respectively. Some AS types that were significantly different in pan-RCC and paracancerous tissues have also been discovered to play a role in carcinoma screening. To sum up, alternative splicing events significantly interfere with the prognosis of patients with pan-RCC and are capable as biomarkers for prognosis.

Highlights

  • Alternative splicing (AS) refers to the fact that a pre-mRNA produces different mRNA splicing isoforms at different splice sites through different splicing methods, which is essential for the regulation of gene expression and the production of protein diversity [1]

  • In KICH, there were a total of 10,226 genes involved in 29,722 AS events, which were identified AS-related genes (ASRGs)

  • We found 2,446 genes in 3,263 Alternate Acceptor site (AA), 2,141 genes in 2,759 Alternate Donor site (AD), 3,489 genes in 3,489 Alternate Promoter (AP), 3,642 genes in 3,642 ATs, 6,542 genes in 13,728 Exon Skip (ES), 155 genes in 157 Mutually Exclusive Exons (ME), and 1,839 genes in 2,684 Retained Intron (RI)

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Summary

Introduction

Alternative splicing (AS) refers to the fact that a pre-mRNA produces different mRNA splicing isoforms at different splice sites through different splicing methods, which is essential for the regulation of gene expression and the production of protein diversity [1]. AS is considered to be the root cause of eukaryotes with significantly fewer genes than protein species. Abnormal AS events will affect tumor cell differentiation, apoptosis, invasion, and metastasis by affecting gene expression products [3]. Even in the absence of genetic mutations, some cancer-associated AS events may lead to carcinogenesis, which may be associated with mutations in the intron splice sites of tumor suppressor genes and become potential therapeutic targets [4]. The study of AS on cancer has becomes a hot area

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