Identification of a ferroptosis-related gene signature for prognosis prediction in colorectal cancer patients and relationship with vitamin D

Abstract

Ferroptosis is a promising colorectal cancer (CRC) treatment strategy; however, its value in prognosis remains at an exploratory stage. Little research has been conducted on vitamin D and ferroptosis, although vitamin D has been shown to inhibit CRC through various mechanisms. A retrospective study was conducted using RNA-seq profiles and corresponding clinical information of CRC patients retrieved from TCGA and GEO databases.We used R package to process and analyze the data. We established the prognostic signature with elastic network regression model. KEGG was used to analyze pathways related to FRGs, and protein-protein interaction(PPI)was used to identify potential interactions with vitamin D. In HCT116 cells, the levels of cysteine (Cys), glutathione (GSH), and reactive oxygen species (ROS) and the expression of ferroptosis marker genes were measured by Western blot and qRT-PCR. Results showed, a prognostic signature containing 39 FRGs was established, and the Area Under Curve (AUC) of the 2nd, 5th, and 8th years were 0.81, 0.81, and 0.78, respectively. There were distinct differences in survival probability between the high- and low-risk groups, and the signature was applicable to stratified survival analysis based on tumor stage. The risk score possessed an independent prognostic value. Importantly, we found that vitamin D receptor (VDR) has a potential relationship with many FRGs, and vitamin D promotes ferroptosis in CRC cells and affects the expression of TP53, MAPK3, and SLC7A11. In summary, a signature with FRGs can effectively predict the prognosis of CRC. Vitamin D can promote ferroptosis in CRC.