Abstract
Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. Indeed, more than 95% of human genes undergo alternative splicing events (ASEs). In this study, we drew an all-around AS profile of thyroid cancer cells based on RNA-seq data. In total, there were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Moreover, 1819 AS signatures were found to be significantly associated with the overall survival (OS) of TC patients. Kaplan–Meier survival analyses suggested that seven types of ASEs were associated with poor prognosis of TC (P < 0.05). Among them, exon skipping (ES) was the most common, with alternate promoter (AP) and alternate terminator (AT) coming second and third, respectively. Our results indicated that acceptor sites (AA) (AUC: 0.937), alternate donor sites (AD) (AUC: 0.965), AT (AUC: 0.964), ES (AUC: 0.999), mutually exclusive exons (ME) (AUC: 0.999), and retained intron (RI) (AUC: 0.837) exhibited an AUC greater than 0.6. In addition, age and risk score (All) were risk factors for TC patients. We also evaluated whether TC-ASEs are regulated by various splicing factors (SFs). We found that the expression of 90 SFs was associated with 469 ASEs and OS of TC patients. Our findings provide an insight into the role of spliceosomes in TC, which may offer novel perspectives in tumor research.
Highlights
Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity
Thyroid cancer can be divided into four pathological types including papillary thyroid cancer (PTC), anaplastic thyroid cancer (ATC), follicular thyroid cancer (FTC), and medullary thyroid cancer (MTC)[4], with papillary thyroid cancer accounting for about 90% of all TC cases[5]
Genome Atlas (TCGA) database, a web-based resource which provides a userfriendly interface for detailed views of alternative mRNA splicing based on the TCGA database and Percent Spliced In (PSI) degrees ranging from 0 to 1 (PSI cutoff used based on false discovery rate (FDR) < 0.05)
Summary
Alternative splicing (AS), a critical post-transcriptional regulatory mechanism, expands gene expression patterns, thereby leading to increased protein diversity. More than 95% of human genes undergo alternative splicing events (ASEs). There were 45,150 AS in 10,446 thyroid cancer cell genes derived from 506 patients, suggesting that ASEs is a common process in TC. Abbreviations TC Thyroid cancer ASEs Alternative splicing events PTC Papillary thyroid carcinoma ATC Anaplastic thyroid carcinoma FTC Follicular thyroid carcinoma MTC Medullary thyroid carcinoma TCGA Cancer genome atlas SFs Splicing factors OS Overall survival. Several studies have reported that aberrant AS is a common event in the development and progression of numerous cancers including gastrointestinal adenocarcinomas and urogenital m alignancies[16,17,18,19]. An all-around AS profile of thyroid cancer was drawn after analyzing RNA-seq data, and prognostic models were developed by combining splicing signatures and clinicopathological parameters. We constructed a splicing network with the overarching goal of providing functional insights into the role of AS in the initiation and development of thyroid cancer
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