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.

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy

“…Recently, signature models using lncRNAs and ferroptosis were established, classifying HCC patients into two groups. The high-risk group had enhanced hepatocarcinogenesis and poor prognosis [ 467 , 468 ]. Equally, non-coding circular RNAs (circRNAs) are associated with the development of HCC through ferroptosis.…”

Role of ferroptosis and its non-coding RNA regulation in hepatocellular carcinoma

“… Wan et al (2022) screen 5 ferroptosis-related markers [G6PD, HMOX1 (heme oxygenase 1), LOX (lysyl oxidase), SLC7A11, and STMN1 (stathmin 1)], which are associated with higher tumor-node-metastasis stage, cirrhosis and immunosuppressive microenvironment in tumor tissue, and further well predict the prognosis of HCC. Studies have found that ferroptosis-related genes serve as independent risk factors to evaluate the clinical efficacy of chemotherapy and immunotherapy in HCC ( Gao R. et al, 2021 ; Xiong et al, 2022 ). The establishment of markers associated with ferroptosis will be beneficial to predict the biological characteristics of HCC and select the optimal therapeutics for HCC patients.…”

“…Further analysis revealed that these prognostic models may regulate HCC immune microenvironment via modulating immune-related pathways, such as the TNF-α/NF-κB and IL-2/STAT5 signaling pathways, which further affects the differentiation of immune infiltration ( Xu Z. et al, 2021 ; Yang X. et al, 2022 ). There are other prediction models showing ferroptosis-related lncRNAs associated with immunity, tumor microenvironment alteration, chemotherapeutic, and immunotherapeutic efficacy in HCC ( Fang et al, 2022 ; Xiong et al, 2022 ). Besides, 17 ferroptosis-associated lncRNAs are identified as a prognostic and risk model for accurate decision making in clinical treatment and immunotherapy of HCC ( Lin and Yang, 2022 ).…”

Comprehensive analysis of cuproptosis-related lncRNAs in immune infiltration and prognosis in hepatocellular carcinoma

“…Liver cancer is among the highest prevalent existing malignancy, leading to approximately 662,000 deaths each year, and its prevalence and death rates are rising year by year globally [ 1 , 2 ]. As the primary histological sub kind of liver cancer, hepatocellular carcinoma (HCC) denotes about 75% of all instances [ 3 ]. Currently, HCC is typically treated with liver resection, liver transplantation, thermal ablation, trans-arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), personalized treatment, and immunotherapy [ 4 , 5 ].…”