Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer

Hui-Yan Wang; Yan Diao; Pei-Zhu Tan; Huan Liang

doi:10.4251/wjgo.v16.i5.1908

Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer

World J Gastrointest Oncol. 2024 May 15;16(5):1908-1924. doi: 10.4251/wjgo.v16.i5.1908.

Authors

Hui-Yan Wang¹, Yan Diao², Pei-Zhu Tan³, Huan Liang⁴

Affiliations

¹ Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin 150086, Heilongjiang Province, China.
² Department of Clinical Laboratory, Heilongjiang Province Hospital, Harbin 150000, Heilongjiang Province, China.
³ Translational Medicine Center of Northern China, Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
⁴ Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin 150086, Heilongjiang Province, China. 601774@hrbmu.edu.cn.

Abstract

Background: As the primary microtubule organizing center in animal cells, centrosome abnormalities are involved in human colon cancer.

Aim: To explore the role of centrosome-related genes (CRGs) in colon cancer.

Methods: CRGs were collected from public databases. Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort. Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature (CRS) to score colon cancer patients. A nomogram was developed to evaluate the CRS risk in colon cancer patients. An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy, chemotherapy, and targeted therapy. Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.

Results: A total of 726 CRGs were collected from public databases. A CRS was constructed, which consisted of the following four genes: TSC1, AXIN2, COPS7A, and MTUS1. Colon cancer patients with a high-risk signature had poor survival. Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+ T cells. Regarding treatment response, patients with a high-risk signature were resistant to immunotherapy, chemotherapy, and targeted therapy. COPS7A expression was relatively high in endothelial cells and fibroblasts. MTUS1 expression was high in endothelial cells, fibroblasts, and malignant cells.

Conclusion: We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients, contributing to the development of individualized treatment for colon cancer.

Keywords: Centrosome; Colon cancer; Immune microenvironment; Prognostic; Signature; Therapy.