Molecular characteristics, clinical significance, and cancer immune interactions of cuproptosis and ferroptosis-associated genes in colorectal cancer

Yang Li; Ru-Yao Wang; Yu-Jiao Deng; Shao-Hua Wu; Xinti Sun; Hong Mu

doi:10.3389/fonc.2022.975859

Molecular characteristics, clinical significance, and cancer immune interactions of cuproptosis and ferroptosis-associated genes in colorectal cancer

Front Oncol. 2022 Sep 5:12:975859. doi: 10.3389/fonc.2022.975859. eCollection 2022.

Authors

Yang Li¹, Ru-Yao Wang², Yu-Jiao Deng³, Shao-Hua Wu¹, Xinti Sun⁴, Hong Mu¹

Affiliations

¹ Department of Clinical Laboratory, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
² Blood Transfusion Department, Qingdao Women and Children's Hospital, Qingdao, China.
³ Department of Clinical Training and Teaching , Tianjin University of Traditional Chinese Medicine, Tianjin, China.
⁴ Department of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Abstract

Objective: To systematically analyze the expression of cuproptosis and ferroptosis genes and their impact on the development, prognosis, tumor microenvironment (TME), and treatment response in colorectal cancer (CRC) patients.

Methods: We systematically evaluated 33 cuproptosis and ferroptosis-related genes and comprehensively identified the correlations between cuproptosis and ferroptosis-related genes and transcriptional patterns, prognosis, and clinical features. Three distinct subgroups were identified in CRC using the TCGA database and the GEO database. We next assessed the relationship between the molecular features, prognostic significance, and clinical indicators of the prognostic genes in the cuproptosis and ferroptosis-related gene clusters. In addition, a PAC_score, which accurately predicted the prognosis of CRC patients and the efficacy of immunomodulatory mAbs, was obtained.

Results: Patients in the low expression group (low expression of cuproptosis and ferroptosis-related genes) had a longer survival compared to the high expression group. We identified two distinct prognosis-associated molecular subtypes and observed an association between clinical information and prognosis. The enrichment analysis of differential genes associated with prognosis showed that the main enrichment was related to biological processes such as metastasis and metabolism. Next, the PCA_score for predicting overall survival (OS) was established and its reliable predictive value in CRC patients was confirmed. Furthermore, highly reliable nomogram was created to facilitate the clinical feasibility of the PCA_score. It was found that the immunomodulatory mAbs, PD-L1 and CTLA4 were highly expressed in the low PCA_score score group with statistically significance.

Conclusion: Overall, the PCA scores of prognostic differential genes in the cuproptosis and ferroptosis-related gene clusters were strongly associated with clinical characteristics, prognosis, and immunotherapy in CRC patients. This data may promote further exploration of more effective immunotherapy strategies for CRC.

Keywords: colorectal cancer; cuproptosis; ferroptosis; nomogram; overall survival.