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Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.

ABSTRACT: Colon cancer is the third most common cancer and the second leading cause of cancer-related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2-like kinase 1(CLK1), CLK2, and A-kinase anchor protein 8-like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low-risk group, and TME-related pathway gene expression was also higher in low-risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.

SUBMITTER: Luo QY

PROVIDER: S-EPMC9530871 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.

Luo Qiu-Yun QY Di Tian T Chen Zhi-Gang ZG Peng Jian-Hong JH Sun Jian J Xia Zeng-Fei ZF Pan Wen-Tao WT Luo Fan F Lu Fei-Teng FT Sun Yu-Ting YT Yang Li-Qiong LQ Zhang Lin L Qiu Miao-Zhen MZ Yang Da-Jun DJ

Cancer science 20220816 10

Colon cancer is the third most common cancer and the second leading cause of cancer-related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified a ...[more]

PMID: 35792657

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Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.

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Novel prognostic model predicts overall survival in colon cancer based on RNA splicing regulation gene expression.

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