Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer

Zhufeng Li; Fang Yuan; Xin Liu; Jianming Wei; Tong Liu; Weidong Li; Chuan Li

doi:10.3389/fonc.2023.1201616

Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer

Front Oncol. 2023 May 23:13:1201616. doi: 10.3389/fonc.2023.1201616. eCollection 2023.

Authors

Zhufeng Li¹, Fang Yuan², Xin Liu¹, Jianming Wei¹, Tong Liu¹, Weidong Li¹, Chuan Li¹

Affiliations

¹ Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
² Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.

Abstract

Background: Ferroptosis, a novel form of regulating cell death, is related to various cancers. However, the role of ferroptosis-related genes (FRGs) on the occurrence and development of colon cancer (CC) needs to be further elucidated.

Method: CC transcriptomic and clinical data were downloaded from TCGA and GEO databases. The FRGs were obtained from the FerrDb database. The consensus clustering was performed to identify the best clusters. Then, the entire cohort was randomly divided into the training and testing cohorts. Univariate Cox, LASSO regression and multivariate Cox analyses were used to construct a novel risk model in training cohort. The testing and the merged cohorts were performed to validate the model. Moreover, CIBERSORT algorithm analyze TIME between high- and low- risk groups. The immunotherapy effect was evaluated by analyzing the TIDE score and IPS between high- and low- risk groups. Lastly, RT-qPCR were performed to analyze the expression of the three prognostic genes, and the 2-years OS and DFS between the high- and low- risk groups of 43 clinical CC samples to further validate the value of the risk model.

Results: SLC2A3, CDKN2A, and FABP4 were identified to construct a prognostic signature. Kaplan-Meier survival curves showed that OS between the high- and low-risk groups were statistically significant (p_merged<0.001, p_training<0.001, p_testing<0.001). TIDE score and IPS were higher in the high-risk group (p_TIDE<0.005, p_Dysfunction<0.005, p_Exclusion<0.001, p_mAb-CTLA-4 = 3e-08, p_mAb-PD-1 = 4.1e-10). The clinical samples were divided into high- and low- risk groups according to the risk score. There was a statistical difference in DFS (p=0.0108).

Conclusion: This study established a novel prognostic signature and provided more insight into the immunotherapy effect of CC.

Keywords: TIME; colon cancer; ferroptosis-related gene; immunotherapy; signature.

Grants and funding

This study is supported by grant from Natural Science Foundation of Tianjin (No. 19JCYBJC27100), Scientific Research Project of Tianjin Education Commission (Natural Science, No. 2017KJ191) and Medical Key Discipline Research Project of Tianjin Medical University General Hospital (ZDXK05202201, ZDXK05202217).