Identification of Key Prognostic Alternative Splicing Events of Costimulatory Molecule-Related Genes in Colon Cancer

Hao Ding; Huiwen Shi; Weifeng Chen; Zhisheng Liu; Zhi Yang; Xiaochuan Li; Zhichao Qiu; Hongqing Zhuo

doi:10.2174/0113862073249972231026060301

Identification of Key Prognostic Alternative Splicing Events of Costimulatory Molecule-Related Genes in Colon Cancer

Comb Chem High Throughput Screen. 2023 Nov 10. doi: 10.2174/0113862073249972231026060301. Online ahead of print.

Authors

Hao Ding¹, Huiwen Shi², Weifeng Chen³, Zhisheng Liu⁴, Zhi Yang⁵, Xiaochuan Li⁶, Zhichao Qiu⁷, Hongqing Zhuo⁸

Affiliations

¹ Department of General Surgery, Huadong Hospital Affiliated to Fudan University, China.
² Department of General Surgery, No. 971 Hospital of PLA Navy, China.
³ Department of Oncology, Huangdao District Hospital of Traditional Chinese Medicine, China.
⁴ Department of General Surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), China.
⁵ The IVD Medical Marketing Department, 3D Medicines Inc., China.
⁶ Department of General Surgery, Qingdao Municipal Hospital, China.
⁷ Department of Oncology, Shunde Hospital, Guangzhou University of Chinese Medicine, China.
⁸ Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong First Medical University, China.

PMID: 37957898
DOI: 10.2174/0113862073249972231026060301

Abstract

Objective: This study aimed to explore the key alternative splicing events in costimulatory molecule-related genes in colon cancer and to determine their correlation with prognosis.

Methods: Gene expression RNA-sequencing data, clinical data, and SpliceSeq data of colon cancer were obtained from The Cancer Genome Atlas. Differentially expressed alternative splicing events in genes were identified, Followed by correlation analysis of genes corresponding to differentially expressed alternative splicing events with costimulatory molecule-related genes. Survival analysis was conducted using differentially expressed alternative splicing events in these genes and a prognostic model was constructed. Functional enrichment, proteinprotein interaction network, and splicing factor analyses were performed.

Results: In total, 6504 differentially expressed alternative splicing events in 3949 genes were identified between tumor and normal tissues. Correlation analysis revealed 3499 differentially expressed alternative splicing events in 2168 costimulatory molecule-related genes. Moreover, 328 differentially expressed alternative splicing events in 288 costimulatory molecule-related genes were associated with overall survival. The prognostic models constructed using these showed considerable power in predicting survival. The ubiquitin A-52 residue ribosomal protein fusion product 1 and ribosomal protein S9 were the hub nodes in the protein-protein interaction network. Furthermore, one splicing factor, splicing factor proline and glutamine-rich, was significantly associated with patient prognosis. Four splicing factor-alternative splicing pairs were obtained from four alternative splicing events in three genes: TBC1 domain family member 8 B, complement factor H, and mitochondrial fission 1.

Conclusion: The identified differentially expressed alternative splicing events of costimulatory molecule-related genes may be used to predict patient prognosis and immunotherapy responses in colon cancer.

Keywords: Colon cancer; alternative splicing; costimulatory molecule; immunotherapy; prognosis.; splicing factor.