Development of a prognostic model based on ferroptosis-related genes for colorectal cancer patients and exploration of the biological functions of NOS2 in vivo and in vitro

Frontiers in Oncology

Oncology

Xiaochuang Feng¹  Yong Hu²  Chengzhi Huang³  Junjiang Wang⁴  Xueqing Yao⁴  Hongming Li⁵ 

[1] Department of Colorectal Surgery, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China;Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China;School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, China;The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China;Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China;The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China;Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China;Department of Colorectal Surgery, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China;

关键词: colorectal cancer;    ferroptosis;    prognostic model;    gene;    NOS2;   

DOI  :  10.3389/fonc.2023.1133946

 received in 2023-02-08, accepted in 2023-05-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundFerroptosis is involved in many malignant tumors and has been implicated in important mechanisms of colorectal cancer (CRC) suppression. However, the prognostic and predictive values of the ferroptosis activation pattern in CRC patients have not been noted. Here, we aimed to construct and validate a prediction model based on ferroptosis-related genes (FRGs) for CRC patients and investigated the expression pattern and biological function of the most significantly altered gene.MethodsA total of 112 FRGs were obtained from the FerrDb website, and the clinical characteristics of 545 CRC patients and their global gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Survival-related FRGs were identified by Cox proportional hazards regression analysis. Finally, the expression pattern and biological function of NOS2, the most implicated gene was explored in vitro and in vivo.ResultsThe prediction model was established based on 8 FRGs. Patients in the high- or low-risk group were stratified based on the median risk value calculated by our model, and patients in the high-risk group experienced poor overall survival (p<0.01). Further validation demonstrated that the FRG model acted as an independent prognostic indicator for CRC patients (HR=1.428, 95% CI, 1.341-1.627; p<0.001). The area under the receiver operating characteristic (ROC) curve (AUC) for 5-year survival was 0.741. NOS2 was one of the most significantly affected FRGs and was highly expressed in malignant tissue, but it inhibited tumor growth and induced tumor cell death in vitro and in vivo, possibly by repressing the NF-κB pathway.ConclusionOur study revealed that FRGs have potential prognostic value in CRC patients and that NOS2 suppresses tumor progression, providing a novel therapeutic target for CRC treatment based on ferroptosis.

【 授权许可】

Unknown   
Copyright © 2023 Li, Feng, Hu, Wang, Huang and Yao