Construction and validation of an immune-related gene signature predictive of survival and response to immunotherapy for colorectal cancer

Chen Li ¹, Mingyang Chen ², Miao Liu ^1,3

⁰Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Medicine +

|

October 28, 2024

View abstract on PubMed

Summary

A new immune-related gene signature accurately predicts colorectal cancer prognosis and immunotherapy response. This signature identifies high-risk patients with advanced disease and poorer immune microenvironments, aiding clinical decisions.

Area Of Science

Oncology
Immunology
Genomics

Background

Colorectal cancer (CRC) is a leading cause of cancer incidence and mortality globally.
Effective prognostic markers and predictors of immunotherapy response are crucial for CRC management.

Purpose Of The Study

To develop and validate an immune-related gene signature for predicting CRC prognosis.
To explore the relationship between the signature and clinical/molecular features, immune infiltration, and immunotherapy response.

Main Methods

Utilized The Cancer Genome Atlas (TCGA) as a training set and GSE39582 as a validation set.
Employed Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression to identify immune-related hub genes.
Constructed a prognostic signature and evaluated its performance using time-dependent ROC curves and calibration plots.
Assessed immune cell infiltration via CIBERSORT and immunotherapy response using immunophenoscore (IPS) and tumor immune dysfunction and exclusion (TIDE) scores.

Main Results

A seven-gene immune-related signature was developed, demonstrating robust prognostic performance in both training and validation cohorts.
The high-risk group, defined by the signature, was associated with advanced disease, unfavorable pathological factors, and a less active immune microenvironment.
The high-risk group showed a predicted poorer response to immunotherapy based on IPS and TIDE scores.

Conclusions

The developed immune-related gene signature effectively predicts prognosis, tumor immune microenvironment, and immunotherapy response in colorectal cancer.
This signature holds potential as a valuable tool for personalized treatment strategies in CRC.