Development and Validation of a Prognostic Model for Colon Cancer Based on Mitotic Gene Signatures and Immune Microenvironment Analysis

Overview

Journal Discov Oncol

Publisher Springer

Specialty Oncology

Date 2024 Oct 9

PMID 39382813

Authors

Changhao Gu

Lulu Jin

Xiaoyan Lv

Cheng Wang

Congle Wen

Xiuxiu Su

Affiliations

Soon will be listed here.

Abstract

Background: Mitotic processes play a pivotal role in tumor progression and immune responses. However, the correlation between mitosis-related genes, clinical outcomes, and the tumor microenvironment (TME) in colon cancer remains unclear. This study aims to develop a prognostic and therapeutic significance model for colon cancer based on mitosis-related genes.

Methods: RNA expression profiles and clinical data of 453 colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Mitosis-related genes were selected from the MsigDb database. The gene model was constructed using differential analysis, univariate and multivariate Cox regression, and Lasso regression analyses. The predictive model was validated using data from the GSE17536, GSE17537, and GSE39582 datasets. Predictive accuracy was evaluated via Receiver Operating Characteristic (ROC) curves, while nomograms were developed by integrating clinical and pathological features. Gene set enrichment analysis explored biological processes and pathways linked to the model. TME was assessed using ESTIMATE, and the proportion and function of immune cells were analyzed through CIBERSORT. Drug sensitivity analysis was conducted using the CTRP database.

Results: A predictive model based on 17 mitosis-related genes (KIFC1, CCNF, EME1, CDC25C, ORC1, CCNJL, ANKRD53, MEIS2, FZD3, TPD52L1, MAPK3, CDKN2A, EDN3, NPM2, PSRC1, INHBA, BIRC5) was created. The model exhibited robust predictive performance across both training and validation cohorts. Nomograms for predicting 3-, 5-, and 7-year survival rates in colon cancer (COAD) patients were generated. The model's correlation with immune cell infiltration and function was highlighted.

Conclusion: The mitosis-related gene model serves as a valuable indicator for predicting survival outcomes in colon cancer patients.

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