Research Paper Volume 11, Issue 19 pp 8270—8293

Systematic profiling of alternative splicing events and splicing factors in left- and right-sided colon cancer

Xiaoliang Huang 1, 2, *, , Jungang Liu 1, 2, *, , Xianwei Mo 1, 2, , Haizhou Liu 3, , Chunyin Wei 1, 2, , Lingxu Huang 1, 2, , Jianhong Chen 1, 2, , Chao Tian 1, 2, , Yongsheng Meng 1, 2, , Guo Wu 1, 2, , Weishun Xie 1, 2, , Franco Jeen P.C. 1, 2, , Zujun Liu 1, 2, , Weizhong Tang 1, 2, ,

  • 1 Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, The People’s Republic of China
  • 2 Guangxi Clinical Research Center for Colorectal Cancer, Nanning 530021, Guangxi Zhuang Autonomous Region, The People’s Republic of China
  • 3 Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, The People’s Republic of China
* Equal contribution

received: April 24, 2019 ; accepted: September 21, 2019 ; published: October 4, 2019 ;

https://doi.org/10.18632/aging.102319
How to Cite

Copyright © 2019 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

LC: left-sided colon cancer; RC: right-sided colon cancer; AS: alternative splicing; SFs: splicing factors; DEAS: differentially expressed alternative splicing; DESFs: differentially expressed splicing factors; PSI: percent-spliced-in; ES: Exon Skip; ME: Mutually Exclusive Exons; RI: Retained Intron; AP: Alternate Promoter; AT: Alternate Terminator; AD: Alternate Donor site; AA: Alternate Acceptor site; ROC: Receiver operating characteristic; DSGs: differentially spliced genes.