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

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

Core Tip: Centrosome abnormalities, as the main microtubule tissue center of animal cells, are associated with human colon cancer. Our aim was to investigate the role of centrosome related genes (CRGs) in colon cancer. A total of 726 CRGs were collected from the public database. We constructed a centrosome-related signature composed of four genes: TSC1, AXIN2, COPS7A, and MTUS1. Colon cancer patients with high-risk characteristics had a low survival rate. Patients with high-risk characteristics exhibited decreased plasma cell levels and memory CD4+ T cell activation. Regarding treatment response, patients with high-risk characteristics were resistant to immunotherapy, chemotherapy, and targeted therapy. The expression of COPS7A was relatively high in endothelial cells and fibroblasts. MTUS1 was highly expressed in endothelial cells, fibroblasts, and malignant cells. We constructed a prognostic marker related to the centrosome, which can accurately predict the prognosis of colon cancer patients and contribute to the development of individualized colon cancer treatment.