Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods

Abstract

Background

As an iron-dependent type of programmed cell death, ferroptosis plays an important role in the pathogenesis and progression of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) have been linked to the prognosis of patients with HCC in a number of studies. Nevertheless, the predictive value of lncRNAs (FRLs) associated with ferroptosis in HCC has not been fully elucidated.

Methods

Download RNA sequencing data and clinical profiles of HCC patients from The Cancer Genome Atlas (TCGA) database. The FRLs associated with prognosis were determined by Pearson's correlation analysis. After that, prognostic signature for FRLs was established using Cox and LASSO regression analyses. Meanwhile, survival analysis, correlation analysis of clinicopathological features, Cox regression, receiver operating characteristic (ROC) curve, and nomogram were used to analyze the FRL signature's predictive capacity. The relationship between signature risk score, immune cell infiltration, and chemotherapy drug sensitivity is further studied.

Results

In total, 93 FRLs were found to be of prognostic value in patients with HCC. A five-FRL signature comprising AC015908.3, LINC01138, AC009283.1, Z83851.1, and LUCAT1 was created in order to enhance the prognosis prediction with HCC patients. The signature demonstrated a good predictive potency, according to the Kaplan-Meier and ROC curves. The five-FRL signature was found to be a risk factor independent of various clinical factors using Cox regression and stratified survival analysis. The high-risk group was shown to be enriched in tumorigenesis and immune-related pathways according to GSEA analysis. Additionally, immune cell infiltration, immune checkpoint molecules, and half-inhibitory concentrations differed considerably between risk groups, implying that this signature could be used to evaluate the clinical efficacy of chemotherapy and immunotherapy.

Conclusion

The five-FRL risk signature is helpful for assessing the prognosis of HCC patients and improving therapy options, so it can be further applied clinically.