IL-6 Promoter Hypomethylation Acts As a Diagnostic Biomarker in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Abstract

BackgroundNew biomarkers are needed to detect hepatocellular carcinoma at an earlier stage and to individualize treatment strategies. IL-6 has been proven to be associated with liver cancer in numerous studies.AimTo evaluate the value of the IL-6 promoter methylation level as a noninvasive biomarker for the diagnosis of liver cancer.MethodsA retrospective analysis of 165 patients with HBV-associated hepatocellular carcinoma (HCC), 198 patients with chronic hepatitis B (CHB) and 31 healthy controls were involved. The methylight was detected the methylation level of the IL-6 promoter in peripheral blood mononuclear cells (PBMCs), clinical and laboratory parameters were obtained.ResultsIL-6 promoter methylation levels were significantly lower in patients with HCC (median 53.59%, interquartile range 52.01–54.75%) than in those with CHB (median 56.05%, interquartile range 54.65–57.67%; P<0.001). The level of IL-6 mRNA in patients with HCC (median 0.371, interquartile range 0.173-0.671) was significantly higher than that in patients with CHB (median 0.203, interquartile range 0.108-0.354; P<0.001) and HCs (median 0.189, interquartile range 0.140-0.262; P=0.001). Meanwhile, the PMR value of IL-6 was notably negatively correlated with the mRNA expression level (Spearman’s R=-0.201, P<0.001). The IL-6 PMR value of HCC patients in age (Spearman’s R=0.193, P=0.026) and TBIL (Spearman’s R=0.186, P=0.032) were very weak correlated. At the same time, the level of IL-6 promoter methylation was also an independent factor in the development of liver cancer. When the IL-6 promoter methylation level was used to diagnose HCC, its detective value was superior to AFP [area under the receiver operating characteristic curve (AUC) 0.773 vs. 0.686, P=0.027], And the combined use of AFP and IL-6 methylation level can improve the area under the receiver operating characteristic curve (p=0.011).ConclusionIL-6 promoter hypomethylation is present in hepatocellular carcinoma, and it may be used as a noninvasive biomarker to detect early liver cancer.

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View

“…In conclusion, the study revealed that in HBV-associated HCC, the methylation levels of the IL-6 promoter were notably lower than those observed in patients with chronic hepatitis B. Conversely, the IL-6 mRNA levels were significantly elevated in HBV-associated HCC compared to both CHB patients and healthy individuals [63].…”

“…The study involved 165 patients diagnosed with HCC associated with hepatitis B virus, 198 patients with chronic hepatitis B, and 31 healthy individuals serving as controls. The research employed Methylight methodology to detect methylation levels in the IL-6 promoter region within peripheral blood mononuclear cells (PBMCs) [63].…”

Silencing of TRAF5 enhances necroptosis in hepatocellular carcinoma by inhibiting LTBR-mediated NF-κB signaling

“…Hepatocellular carcinoma (HCC), a common malignancy, is one of the dominant causes of cancer-associated deaths worldwide ( Khemlina, Ikeda & Kurzrock, 2017 ). It has been reported that HCC accounts for approximately 90% of liver cancer, with a prevalence rate of 4.7% of all tumors and a mortality rate of 8.3% worldwide ( Yang et al, 2022 ). Currently, surgical resection, transplantation, and ablation are the standard therapeutic strategies for early-stage HCC ( Huang et al, 2022 ).…”