Abstract

Background Ferroptosis has been found to play an essential role in cancers. Nevertheless, few studies have focused on ferroptosis-related long non-coding RNAs (lncRNAs) in colon cancer. Especially, the association between ferroptosis-related lncRNAs (FeRLs) and the tumor microenvironment (TME) remains unknown. This study aimed to develop a signature based on FeRLs and explore its correlation with the TME in colon cancer. Methods In the current study, we downloaded RNA sequencing (RNA-seq) and clinical data for patients with colon cancer from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was performed to identify FeRLs. Then, we constructed a prognostic signature using univariate and multivariate Cox regression analyses. Subsequently, we assessed the predictive value of the signature in terms of prognosis and treatment response. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to confirm the expression pattern of FeRLs. Results Nine FeRLs were used to construct the predictive signature. A higher risk score based on the signature was associated with a poorer prognosis. Subsequently, we established an accurate nomogram for stratifying patients at high risk, combining the risk model with clinical characteristics. Moreover, single sample gene set enrichment analysis (ssGSEA) analyses showed that the TME status differed significantly between the high- and low-risk groups. Surprisingly, we found that the high-risk group tended to show stromal activation. Importantly, the low-risk group was closely associated with better immunotherapeutic and chemotherapeutic responses. Validation through qRT-PCR confirmed the differential expression of these FeRLs in colon cancer cells compared to normal colon cells. Conclusions We established a novel signature based on nine FeRLs, which displayed satisfactory capacity in predicting prognosis for colon cancer.