Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.1908
Peer-review started: November 7, 2023
First decision: December 28, 2023
Revised: January 8, 2024
Accepted: February 22, 2024
Article in press: February 22, 2024
Published online: May 15, 2024
Processing time: 184 Days and 11.3 Hours
Centrosome abnormalities play a significant role in the development of human colon cancer, as they serve as the primary microtubule organizing center in animal cells.
The primary aim of this investigation was to explore the role of centrosome-related genes (CRGs) in the pathogenesis of colon cancer.
To examine the role of CRGs in the pathogenesis of colon cancer.
CRGs were obtained from publicly available databases. Subsequently, consensus clustering analysis was conducted to partition the Cancer Genome Atlas (TCGA)-Colon adenocarcinoma cohort. Univariate Cox and least absolute shrinkage selection operator regression analyses were employed to identify potential prognostic CRGs and establish a centrosome-related signature (CRS) for scoring patients with colon cancer. Furthermore, a nomogram was devised to assess the risk associated with the CRS in individuals diagnosed with colon cancer. A bioinformatics analysis was integrated to investigate the association between the CRS and tumor immune microenvironment, as well as the response to immunotherapy, chemotherapy, and targeted therapy. Furthermore, a single-cell transcriptome analysis was performed to examine the immune cell composition of key prognostic genes.
A cumulative count of 726 colorectal CRGs was obtained from publicly available databases. Subsequently, a colorectal cancer risk signature was developed, comprising four specific genes, namely TSC1, AXIN2, COPS7A, and MTUS1. Notably, patients with a high-risk signature exhibited unfavorable survival outcomes. Furthermore, these patients demonstrated reduced levels of plasma cells and activated memory CD4+ T cells. In terms of therapeutic response, individuals with a high-risk signature displayed resistance to immunotherapy, chemotherapy, and targeted therapy. Additionally, COPS7A expression was found to be relatively elevated in endothelial cells and fibroblasts. The expression of MTUS1 was observed to be significantly elevated in endothelial cells, fibroblasts, and malignant cells.
In light of these findings, we endeavored to develop a prognostic signature associated with CRGs that could effectively forecast the prognosis of patients with colon cancer. By doing so, we aimed to contribute to the advancement of personalized treatment strategies for individuals diagnosed with colon cancer.
This model has the potential to enhance the individualized approach to colon cancer management.