Xuanlong Du1, Yewei Zhang1. 1. Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses around the world. Ferroptosis is a new form of cell death, and some studies have found that it is related to cancer immunotherapy. The aim of our research was to find immunity- and ferroptosis-related biomarkers to improve the treatment and prognosis of HCC by bioinformatics analysis. METHODS: First, we obtained the original RNA sequencing (RNA-seq) expression data and corresponding clinical data of HCC from The Cancer Genome Atlas (TGCA) database and performed differential analysis. Second, we used immunity- and ferroptosis-related differentially expressed genes (DEGs) to perform a computational difference algorithm and Cox regression analysis. Third, we explored the potential molecular mechanisms and properties of immunity- and ferroptosis-related DEGs by computational biology and performed a new prognostic index based on immunity- and ferroptosis-related DEGs by multivariable Cox analysis. Finally, we used HCC data from International Cancer Genome Consortium (ICGC) data to perform validation. RESULTS: We obtained 31 immunity (p < 0.001)- and 14 ferroptosis (p < 0.05)-related DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Then, we screened five immunity- and two ferroptosis-related DEGs (HSPA4, ISG20L2, NRAS, IL17D, NDRG1, ACSL4, and G6PD) to establish a predictive model by multivariate Cox regression analysis. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses demonstrated a good performance of the seven-biomarker signature. Functional enrichment analysis including Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the seven-biomarker signature was mainly associated with HCC-related biological processes such as nuclear division and the cell cycle, and the immune status was different between the two risk groups. CONCLUSION: Our results suggest that this specific seven-biomarker signature may be clinically useful in the prediction of HCC prognoses beyond conventional clinicopathological factors. Moreover, it also brings us new insights into the molecular mechanisms of HCC.
BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses around the world. Ferroptosis is a new form of cell death, and some studies have found that it is related to cancer immunotherapy. The aim of our research was to find immunity- and ferroptosis-related biomarkers to improve the treatment and prognosis of HCC by bioinformatics analysis. METHODS: First, we obtained the original RNA sequencing (RNA-seq) expression data and corresponding clinical data of HCC from The Cancer Genome Atlas (TGCA) database and performed differential analysis. Second, we used immunity- and ferroptosis-related differentially expressed genes (DEGs) to perform a computational difference algorithm and Cox regression analysis. Third, we explored the potential molecular mechanisms and properties of immunity- and ferroptosis-related DEGs by computational biology and performed a new prognostic index based on immunity- and ferroptosis-related DEGs by multivariable Cox analysis. Finally, we used HCC data from International Cancer Genome Consortium (ICGC) data to perform validation. RESULTS: We obtained 31 immunity (p < 0.001)- and 14 ferroptosis (p < 0.05)-related DEGs correlated with overall survival (OS) in the univariate Cox regression analysis. Then, we screened five immunity- and two ferroptosis-related DEGs (HSPA4, ISG20L2, NRAS, IL17D, NDRG1, ACSL4, and G6PD) to establish a predictive model by multivariate Cox regression analysis. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses demonstrated a good performance of the seven-biomarker signature. Functional enrichment analysis including Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the seven-biomarker signature was mainly associated with HCC-related biological processes such as nuclear division and the cell cycle, and the immune status was different between the two risk groups. CONCLUSION: Our results suggest that this specific seven-biomarker signature may be clinically useful in the prediction of HCC prognoses beyond conventional clinicopathological factors. Moreover, it also brings us new insights into the molecular mechanisms of HCC.
Authors: Sonja Sibold; Vincent Roh; Adrian Keogh; Peter Studer; Céline Tiffon; Eliane Angst; Stephan A Vorburger; Rosemarie Weimann; Daniel Candinas; Deborah Stroka Journal: FEBS Lett Date: 2007-02-07 Impact factor: 4.124
Authors: Jessalyn M Ubellacker; Alpaslan Tasdogan; Vijayashree Ramesh; Bo Shen; Evann C Mitchell; Misty S Martin-Sandoval; Zhimin Gu; Michael L McCormick; Alison B Durham; Douglas R Spitz; Zhiyu Zhao; Thomas P Mathews; Sean J Morrison Journal: Nature Date: 2020-08-19 Impact factor: 49.962