Molecular subtype identification and prognosis stratification by a immunogenic cell death-related gene expression signature in colorectal cancer

ABSTRACT

Objectives

This study intended to develop a new immunogenic cell death (ICD)-related prognostic signature for colorectal cancer (CRC) patients.

Research design and methods

The Non-Negative Matrix Factorization (NMF) algorithm was adopted to cluster tumor samples based on ICD gene expression to obtain ICD-related subtypes. Survival analysis and immune microenvironment analysis were conducted among different subtypes. Regression analysis was used to construct the model. Based on riskscore median, cancer patients were classified into high and low risk groups, and independent prognostic ability of the model was analyzed. The CIBERSORT algorithm was adopted to determine the immune infiltration level of both groups.

Results

We analyzed the differential genes between cluster 4 and cluster 1–3 and obtained 12 genes with the best prognostic features finally (NLGN1, SLC30A3, C3orf20, ADAD2, ATOH1, ATP6V1B1, KCNQ2, MUCL3, RGCC, CLEC17A, COL6A5, and INSL4). In addition, patients with lower risk had higher levels of infiltration of most immune cells, lower Tumor Immune Dysfunction and Exclusion (TIDE) level and higher immunophenscore (IPS) level than those with higher risk.

Conclusions

This study constructed and validated the ICD feature signature predicting CRC prognosis and provide a reference criteria for guiding the prognosis and immunotherapy of CRC cancer patients.

KEYWORDS:

• Colorectal cancer
• immunogenicity
• clustering
• prognostic signature
• immunity

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethical approval

Ethical approval and consent were not required as this study was based on publicly available data.

Authors’ contributions

JPL and JF conceived and designed the study. JPL, TYW and YG performed the experiments.

MMG, TX, SS and LC provided the mutants. YX and BHL wrote the paper. JPL, JF and LC reviewed and edited the manuscript. All authors read and approved the manuscript.

Availability of data and materials

The date and materials in the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737140.2024.2320187.

Additional information

Funding

The study was sponsored by Innovative Research Program of Xiangyang No.1 People’s Hospital, Grant/Award Number: XYY2023QA09; The Scientific and Technological Project of Xiangyang City of Hubei Province, Grant/Award Number: 2021YL24.