Establishment And Validation Of A Ferroptosis-Related LncRNA Prognostic Model In Colorectal Cancer Based On Bioinformatics Analysis

Colorectal cancer(CRC)is the most widespread intestinal malignant tumor.LncRNAs play multiple functions in the tumorigenesis,development,and relapse of CRC.As a new regulatory pattern of cell death that depends on iron and lipid peroxidation,ferroptosis has also been reported to play a pivotal role in the occurrence and development of tumors.It has been reported that lncRNAs are involved in the process of ferroptosis and inhibit the occurrence and progression of CRC.Nonetheless,the relevance between lncRNAs and ferroptosis,as well as their prognostic roles for CRC,remains largely unknown.In this study,we aim to construct a prognostic model that can accurately predict the prognosis of CRC patients.Firstly,we identified the lncRNAs related to ferroptosis based on the RNA sequencing(RNA-seq)data of CRC from the TCGA database.Then,we identified an entire set and divided it into the training and test sets.The univariate Cox regression analysis was used to detect ferroptosis-related lncRNAs associated with the prognosis of the CRC patients in the training set.The LASSO and multivariate Cox regression analyses were then used to establish a prognostic model composed of 8 ferroptosisrelated lncRNAs in training set,including LINC01857,CCDC144NL-AS1,AP003555.1,AL161729.4,AC010973.2,AC009549.1,AC099850.3,and AC008494.3.Next,we calculated the risk score of each CRC patient.Furthermore,we divided the CRC patients into high-and low-risk groups by the risk score and found the overall survival(OS)of patients in the high-risk group was significantly shorter than that of the low-risk group by the Kaplan-Meier analysis.The receiver operator characteristic(ROC)analysis proved that the lncRNA model has good accuracy in predicting prognosis of patients.Besides,the patients in the high-risk group had lower recurrence-free survival(RFS),disease free survival(DFS),disease-specific survival(DSS),and progression free survival(PFS),and progression-free interval(PFI)than these of patients in the low-risk group.We then further proved the above results in the test set and entire set.Moreover,our lncRNA model demonstrated broad applicability in various clinical subgroups.The risk score of lncRNA model could serve as an independent prognostic factor for CRC patients.Additionally,we have constructed and verified a nomogram that can effectively predict the OS rate of CRC patients.Notably,the functional enrichment analysis based on RNA-seq data showed the cancer metastasis-related pathways were enriched in the high-risk group,whereas the ferroptosis pathway that probably suppressed CRC progression was enriched in the low-risk group.Based on the proteomic data and mutation data,functional enrichment analysis further demonstrated that the oncogenic pathways were enriched in the high-risk group.In summary,our lncRNA model can not only provide accurate judgment of CRC prognosis but also possess potential as guidance for clinical decision-making.