Identification of PIF1 as a Ferroptosis-Related Prognostic Biomarker Correlated with Immune Infiltration in Hepatocellular Carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is a primary liver malignancy characterized by high morbidity and mortality. Recently, ferroptosis has been recognized as an important factor in regulating cell growth in HCC. However, the role of ferroptosis-related genes in HCC remains unclear. The SRP119173 dataset from the Sequence Read Archive database was used to screen differentially expressed genes (DEGs) related to ferroptosis. Meanwhile, weighted gene co-expression network analysis was conducted to identify the HCC-related gene modules in the TCGA-liver hepatocellular carcinoma (LIHC) cohort. Next, the candidate genes related to HCC progression and ferroptosis were identified by Venn analysis. Kaplan-Meier, multivariate COX regression, and CIBERSORT analyses were then performed. Our results found that the levels of PIF1 5'-to-3' DNA helicase (PIF1) were notably elevated in HCC tissues relative to normal tissues. Additionally, HCC patients with high PIF1 expression had worse overall survival outcomes than patients with low PIF1 expression. Additionally, the PIF1 gene could independently predict HCC patients' prognosis. Meanwhile, HCC patients with high PIF1 levels had a higher proportion of regulatory T cells (Tregs) and M0 macrophages, as well as higher expression of immune checkpoints such as PD-1 (PDCD1) and PD-L1 (CD274), compared with patients with low PIF1 levels. Our data suggested that a ferroptosis-related gene PIF1 may serve as a potential biomarker for predicting prognosis in HCC patients.