The construction of a novel ferroptosis-related lncRNA model to predict prognosis in colorectal cancer patients.

Abstract

Colorectal cancer (CRC) is the most common gastrointestinal tumor with poor prognosis. Ferroptosis is a pivotal form of programmed iron-dependent cell death different from autophagy and apoptosis, and long noncoding RNA (lncRNA) can influence the prognosis of CRC via regulating ferroptosis. To explore the role and prognostic value of the constructed ferroptosis-related lncRNA model in CRC, a prognostic model was constructed and validated by screening ferroptosis-related lncRNAs associated with prognosis based on the transcriptome data and survival data of CRC patients in The Cancer Genome Atlas database. Regarding the established prognostic models, differences in signaling pathways and immune infiltration, as well as differences in immune function, immune checkpoints, and N6-methyladenosine-related genes were also analyzed. A total of 6 prognostic ferroptosis-related lncRNAs were obtained, including AP003555.1, AC010973.2, LINC01857, AP001469.3, ITGB1-DT and AC129492.1. Univariate independent prognostic analysis, multivariate independent prognostic analysis and receiver operating characteristic curves showed that ferroptosis-related lncRNAs could be recognized as independent prognostic factors. The Kaplan-Meier survival curves and the risk curves showed that the survival time of the high-risk group was shorter. Gene set enrichment analysis enrichment analysis showed that ATP-binding cassette transporters, taste transduction and VEGF signaling pathway were more active in high-risk groups that than in low-risk groups. However, the citrate cycle tricarboxylic acid cycle, fatty acid metabolism and peroxisome were significantly more active in the low-risk group than in the high-risk group. In addition, there were also differences in immune infiltration in the high-low-risk groups based on different methods, including antigen-presenting cell co-stimulation, chemokine receptor, parainflammation, and Type II IFN Response. Further analysis of Immune checkpoints showed that most of the Immune checkpoints such as TNFRSF18, LGALS9 and CTLA4 in the high-risk group were significantly higher than those in the low-risk group, and the expressions of N6-methyladenosine related genes METTL3, YTHDH2 and YTHDC1 were also significantly different in the high-risk group. Ferroptosis-related lncRNAs are closely related to the survival of colorectal cancer patients, which can be used as new biomarkers and potential therapeutic targets for the prognosis of colorectal cancer.