Identification of signature of tumor-infiltrating CD8 T lymphocytes in prognosis and immunotherapy of colon cancer by machine learning

Kaili Liao; Qijun Yang; Yuhan Xu; Yingcheng He; Jingyi Wang; Zimeng Li; Chengfeng Wu; Jialing Hu; Xiaozhong Wang

doi:10.1016/j.clim.2023.109811

Identification of signature of tumor-infiltrating CD8 T lymphocytes in prognosis and immunotherapy of colon cancer by machine learning

Clin Immunol. 2023 Dec:257:109811. doi: 10.1016/j.clim.2023.109811. Epub 2023 Oct 18.

Authors

Kaili Liao¹, Qijun Yang², Yuhan Xu², Yingcheng He², Jingyi Wang³, Zimeng Li³, Chengfeng Wu⁴, Jialing Hu⁵, Xiaozhong Wang⁶

Affiliations

¹ Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Jiangxi Province Key Laboratory of Laboratory Medicine, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, No. 1 Minde Road, Nanchang, Jiangxi 330006, China.
² Queen Mary College of Nanchang University, Xuefu Road, Nanchang, Jiangxi 330001, China.
³ School of Public Health of Nanchang University, Nanchang, Jiangxi 330001, China.
⁴ Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi 330006, China.
⁵ Department of Emergency, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi 330006, China.
⁶ Department of Clinical Laboratory, the Second Affiliated Hospital of Nanchang University, Jiangxi Province Key Laboratory of Laboratory Medicine, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, No. 1 Minde Road, Nanchang, Jiangxi 330006, China. Electronic address: wangxzlj@126.com.

PMID: 37858752
DOI: 10.1016/j.clim.2023.109811

Abstract

Background: To explore the specific marker of CD8+ T cell subsets which are closely related to the prognosis and immunotherapy of patients with colon cancer.

Methods: 18 kinds of immune cell expression profile data sets were obtained from GEO database. Compared with other immune cell types, the specific markers of CD8 (+) T cells (TI-CD8) in colorectal cancer were screened. Regression analyses were used to further screen prognostic related genes and construct a prognostic evaluation model. The patients were stratified and analyzed according to the risk scores, KRAS mutation status, stage, lymphatic infiltration and other indicators. The landscape of infiltration level, mutation and copy number variation of immune subsets in high and low TI-CD8Sig score groups were compared and analyzed. The difference of drug response between high and low TI-CD8Sig score groups was analyzed. Differential expression of the model genes was verified by the HPA database.

Results: Six prognostic-related CD8T cell-specific gene targets were further screened, and the prognostic evaluation model was constructed. The AUC value of the model is >0.75. FAT3 and UNC13C showed a high mutation state in the low-risk group, while USH2A, MUC5B et al. specifically showed a high mutation state in the high-risk group. Compared with the low-risk group, the high-risk group had lower effective rate of drug response. The expression of PD-1 gene was positively correlated with the level of TI-CD8Sig score.

Conclusion: The risk assessment model based on CD8T cell-specific marker genes can effectively predict the prognosis and the drug response of patients with CRC.

Keywords: Immunotherapy; Machine learning; Prognosis; Tumor-infiltrating CD8 T lymphocytes; colon cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
Colonic Neoplasms* / genetics
Colonic Neoplasms* / therapy
DNA Copy Number Variations*
Humans
Immunotherapy
Machine Learning
Prognosis
Tumor Microenvironment