A novel anoikis-related gene prognostic signature and its correlation with the immune microenvironment in colorectal cancer

Frontiers in Genetics

Genetics

Peicheng Lin¹  Qian Wu¹  Yiran Chen¹  Libin Liu¹  Hui Li¹  Yu Xiao¹  Jinluan Li¹  Han Zhou¹  Junxin Wu²  Lirui Tang³ 

[1] Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China;[e-mail];null;

关键词: colorectal cancer;    anoikis;    tumor microenvironment;    immunotherapy;    prognosis;   

DOI  :  10.3389/fgene.2023.1186862

 received in 2023-03-15, accepted in 2023-05-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Anoikis is a type of apoptosis associated with cell detachment. Resistance to anoikis is a focal point of tumor metastasis. This study aimed to explore the relationship among anoikis-related genes (ARGs), immune infiltration, and prognosis in colorectal cancer (CRC).Methods: The transcriptome profile and clinical data on patients with CRC were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Patients were divided into two clusters based on the expression of ARGs. Differences between the two ARG molecular subtypes were analyzed in terms of prognosis, functional enrichment, gene mutation frequency, and immune cell infiltration. An ARG-related prognostic signature for predicting overall survival in patients with CRC was developed and validated using absolute value convergence and selection operator (LASSO) regression analysis. The correlation between the signature risk score and clinicopathological features, immune cell infiltration, immune typing, and immunotherapy response was analyzed. The risk score combined with clinicopathological characteristics was used to construct a nomogram to assess CRC patients’ prognosis.Results: Overall, 151 ARGs were differentially expressed in CRC. Two ARG subtypes, namely, ARG-high and ARG-low groups, were identified and correlated with CRC prognosis. The gene mutation frequency and immune, stromal, and ESTIMATE scores of the ARG-high group were higher than those of the ARG-low group. Moreover, CD8, natural killer cells, M1 macrophages, human leukocyte antigen (HLA), and immune checkpoint-related genes were significantly increased in the ARG-high group. An optimized 25-gene CRC prognostic signature was successfully constructed, and its prognostic predictive ability was validated. The high-risk score was correlated with T, N, M, and TNM stages. Risk scores were negatively correlated with dendritic cells, eosinophils, and CD4 cells, and significantly positively correlated with regulatory T cells. Patients in the high-risk group were more likely to exhibit immune unresponsiveness. Finally, the nomogram model was constructed and showed good prognostic predictive power.Conclusion: ARGs are associated with clinicopathological features and the prognosis of CRC, and play important roles in the immune microenvironment. Herein, we underpinned the usefulness of ARGs in CRC to develop more effective immunotherapy techniques.

【 授权许可】

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Copyright © 2023 Xiao, Zhou, Chen, Liu, Wu, Li, Lin, Li, Wu and Tang.