Systematic Profiling of Alternative Splicing Events and Splicing Factors in Left- And Right-Sided Colon Cancer

Aging (Albany NY). 2019 Oct 4;11(19):8270-8293. doi: 10.18632/aging.102319. Epub 2019 Oct 4.

Abstract

Left- and right-sided colon cancer (LC and RC) differ substantially in their molecular characteristics and prognoses, and are thus treated using different strategies. We systematically analyzed alternative splicing (AS) events and splicing factors in LC and RC. RNA-seq data were used for genome-wide profiling of AS events that could distinguish LC from RC. The Exon Skip splicing pattern was more common in RC, while the Retained Intron pattern was more common in LC. The AS events that were upregulated in RC were enriched for genes in the axon guidance pathway, while those that were upregulated in LC were enriched for genes in immune-related pathways. Prognostic models based on differentially expressed AS events were built, and a prognostic signature based on these AS events performed well for risk stratification in colon cancer patients. A correlation network of differentially expressed AS events and differentially expressed splicing factors was constructed, and RBM25 was identified as the hub gene in the network. In conclusion, large differences in AS events may contribute to the phenotypic differences between LC and RC. The differentially expressed AS events reported herein could be used as biomarkers and treatment targets for colon cancer.

Keywords: FIP1L1; SATB2; TCGA; prognostic signature; splicing factor.

Publication types

  • Research Support, Non-U.S. Gov't