Long Non-Coding RNA Signatures Associated with Ferroptosis Predict Prognosis in Colorectal Cancer

Currently, colorectal cancer has become a common gastrointestinal malignancy that usually occurs in the colon and rectum, and ferroptosis plays a vital role in the pathology and progression of colorectal tumors.

A total of 627 patients (51 normal and 644 tumor samples) from The Cancer Genome Atlas (TCGA)-COAD and TCGA-READ were included in the study. Lasso and Cox's regression was employed to analyze the characteristic lncRNAs in colorectal cancer samples, and a distinctive prognostic model of ferroptosis-related lncRNAs was established. By analyzing the divergence between the high and low-risk groups of ferroptosis-related lncRNAs, 15 characteristic lncRNAs related to the prognosis of colorectal cancer were evaluated. Kaplan-Meier analysis, operation characteristic curve (ROC), nomogram, and gene set enrichment analyses (GSEA) further confirmed the validity of the characteristic prognostic model with ferroptosis-related lncRNAs.

Kaplan-Meier analysis confirmed a high-risk group of ferroptosis-related lncRNA interrelated with a poor prognosis in colorectal cancer. AUC estimates of 1 -, 3 -, and 5-year survival rates for ferroptosis-related lncRNA characteristic models were 0.745, 0.767 and 0.789. GSEA analysis showed that immune and malignancy-related pathways were active in the high-risk score group. In addition, differential analyses of immune function, including Checkpoint, cytolytic, HLA, and T cell co-inhibition, differed significantly betwixt low - and high-risk groups.CD160, TNFRSF18, CD27, PDCD1, CD200R1, ADORA2A, TNFRSF14, LAIR1, CD244, CD40, TNFRSF4, CD70, TNFSF14, TNFRSF25, CD276, HHLA2, VTCN1, LAG3, TNFSF18, and other immune checkpoints had different expressions betwixt the high- and low-risk group.

Fifteen kinds of lncRNAs with different expressions (AP003555.1, AC099850.3, AL031985.3, LINC01857, STPG3-AS1, AL137782.1, AC124067.4, AC012313.5, AC083900.1, AC010973.2, ALMS1-IT1, AC013652.1, AC133540.1, AP006621.2, AC018653.3) were closely associated with poor prognosis of colorectal cancer. These indicators were significantly correlated with the overall survival (OS) rate and could be used as prognostic evaluation criteria.