The necroptosis related gene LGALS3 can be used as a biomarker for the adverse progression from chronic HBV infection to HCC

Abstract

The number of patients with hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection remains large, despite the remarkable effectiveness of antiviral drugs and vaccines for HBV in preventing and treating HBV infection. Necroptosis is closely related to the occurrence of inflammation, clearance of viral infection, and tumor progression. Presently, little is known about the changes in necroptosis-related genes in the progression from chronic HBV infection (CHI) to HBV-related hepatic fibrosis (HBV-HF) and HBV-related hepatocellular carcinoma (HBV-HCC). In this study, Cox regression analysis was performed using GSE14520 chip data and a necroptosis-related genes survival prognosis score (NRGPS) was established for HBV-HCC patients. NRGPS was constructed using three model genes (G6PD, PINK1 and LGALS3), and verified by data sequencing in the TCGA database. The HBV-HCC cell model was established by transfection of pAAV/HBV1.2C2, constructed by homologous recombination, into HUH7 and HEPG2 cells. The expression levels of G6PD, PINK1, and LGALS3 were detected using RT-qPCR. We further analyzed the expression of the model genes in GSE83148, GSE84044, and GSE14520 and found that LGALS3 was consistently highly expressed in CHI, high fibrosis score and high NRGPS. In addition, immune microenvironment analysis showed that LGALS3 was not only associated with the infiltration of regulatory T cells in the immune microenvironment but also with expression of CCL20 and CCR6. The expression levels of model genes, FOXP3 and CCR6, were analyzed using RT-qPCR in peripheral blood mononuclear cells of 31 hepatitis B surface antibody positive patients, 30 CHI, 21 HBV-HF, and 20 HBV-HCC. In further cell-model experiments, we analyzed the expression of CCL20 by RT-qPCR and the changes in cell proliferation and migration by CCK8 and transwell assays, respectively, in HBV-HCC cell models after LGALS3 knockdown. The findings of this study suggest that LGALS3 could be a biomarker for adverse progression following chronic HBV infection and may also be involved in the regulation of the immune microenvironment, making it a potential therapeutic target.

Comprehensive assessment of regulatory T-cells-related scoring system for predicting the prognosis, immune microenvironment and therapeutic response in hepatocellular carcinoma

“…LAPTM4B as a risk factor in a scoring system which has been shown to induce autophagy and promote tumour growth in HCC [ 38 ]. LGALS3 has been shown to be used as a potential biomarker for the malignant progression of HBV infection to HCC and is thought to be associated with necroptosis in HCC [ 39 ]. Notably, the role of RPS8 in HCC has not been elucidated, and given the prognostic predictive value of TRSSys for HCC, its regulatory mechanism in HCC warrants further subsequent exploration.…”

Galectin-3-ITGB1 Signaling Mediates Interleukin 10 Production of Hepatic Conventional Natural Killer Cells in Hepatitis B Virus Transgenic Mice and Correlates with Hepatocellular Carcinoma Progression in Patients

“…Gal-3 has been closely associated with a poor prognosis of primary HCC, by promoting tumor cell growth, migration and invasion, stimulating angiogenesis and enhancing the tumorigenesis and metastasis of HCC cells [24,42,43]. After persistent HBV infection, Gal-3 was demonstrated to play a key role in adverse disease progression and to be a potential therapeutic target [44]. In this study, LGALS3 expression was negatively correlated with the overall survival of HCC patients (Figure 8C), which was consistent with the levels of ITGB1 and IL-10 (Figure S3).…”

The Characteristics of Transcription Factors Regulating T Cell Exhaustion Were Analyzed to Predict the Prognosis and Therapeutic Effect in Patients with HCC

“…Dong et al established a prognosis score for patients with HBV-HCC based on necroptosis related genes, effectively stratified the patients’ prognosis, and found that LGALS3 could be used as a biomarker for the adverse progression of chronic HBV infection. 46 Therefore, it is reasonable and promising to build predictive models or discover biomarkers based on database big data and verify them. Recently, Zhong et al established a risk score model from the perspective of anoikis, which was externally verified by ICGC cohort but not internally verified in TCGA cohort.…”