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Human leukocyte antigen gene polymorphisms are associated with systemic inflammation in hepatitis B virus-related hepatocellular carcinoma.

ABSTRACT: Background:Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. Patients and methods:This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. Results:The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P<0.05). The rs7453920 genotype was significantly associated with the neutrophil/lymphocyte ratio (NLR; P=0.001), which was used as an SI index with a threshold determined by receiver operating characteristic analysis. An elevated NLR was also an independent predictor of OS according to univariate and multivariate analyses (P<0.001). Conclusion:Our data show that HLA gene polymorphisms are associated with SI in patients with HBV-related HCC, and the absence of minor allele A (rs7453920) promotes SI and shortens OS.

SUBMITTER: Wu XL

PROVIDER: S-EPMC6074760 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Human leukocyte antigen gene polymorphisms are associated with systemic inflammation in hepatitis B virus-related hepatocellular carcinoma.

Wu Xiao-Long XL Li Zhi-Yu ZY Bi Xin-Yu XY Zhao Hong H Zhao Jian-Jun JJ Zhou Jian-Guo JG Han Yue Y Huang Zhen Z Zhang Ye-Fan YF Cai Jian-Qiang JQ

Cancer management and research 20180731

<h4>Background</h4>Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI.<h4>Patients and methods</h4>This ...[more]

PMID: 30104900

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Project description:BackgroundThere is basic research suggesting that Huaier granule can inhibit liver cirrhosis and hepatocellular carcinoma (HCC), but this conclusion has not been clinically verified. We analyzed the distant cancer tissue of two groups of hepatitis B virus (HBV) related HCC with/without Huaier granule, to clarify the effect of Huaier granule on liver inflammation, liver fibrosis, and postoperative recurrence.MethodsWe collected clinicopathological data of HCC patients who received two surgery procedures at Mengchao Hepatobiliary Hospital of Fujian Medical University in China from January 2014 to December 2020. Patients according to taking/not taking Huaier granule after the first hepatectomy were divided into two groups, 51 patients with Huaier granule for more than 6 months after operation (Group A); 56 patients without Huaier granule (Group B). The effects on liver inflammation, fibrosis grade, and postoperative recurrence were compared between two groups.ResultsThe results showed that liver inflammation improved significantly in the Group A [19 (37.3%) cases improved, 31 (60.8%) cases remained unchanged, and 1 (2.0%) case deteriorated] was significantly more than that in the Group B [7 (12.5%) cases improved, 32 (57.1%) cases remained unchanged, and 17 (30.4%) cases deteriorated] (P<0.001). The liver fibrosis in the Group A [17 (33.3%) cases improved, 32 (62.7%) cases remained unchanged, and 2 (3.9%) cases deteriorated] was significantly improved in the Group B [5 (8.9%) cases improved, 45 (80.4%) cases remained unchanged, and 6 (10.7%) cases deteriorated] (P=0.005). The recurrence interval (27.0±21.2 months) in the Group A was significantly longer than that in the Group B (19.0±14.2 months) (P=0.026).ConclusionsHuaier granule can improve liver inflammation, fibrosis, and liver function and prolong the time to recurrence in HBV-related HCC. Given the high rate of postoperative recurrence and poor prognosis of HBV-related HCC, our findings may have useful clinical significance in the prevention of tumor recurrence in these patients.

Project description:Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including HCC. In this study, we analyzed aberrant promoter methylation on genome-wide scale in 6 HCCs including 3 HBV-related and 3 HCV-related HCCs, 6 matched noncancerous liver tissues and 3 normal liver tissues by methylated DNA immunoprecipitation-on-chip analysis. Candidate genes with promoter methylation were detected more frequently in HCV-related HCC. Candidate genes methylated preferentially to HBV-related or HCV-related HCCs were detected and selected, and methylation levels of the selected genes were validated using 125 liver tissue samples, including 61 HCCs (28 HBV-related HCCs and 33 HCV-related HCCs) and matched 59 matched noncancerous livers, and 5 normal livers, by quantitative methylation analysis using MALDI-TOF mass spectrometry. Among analyzed genes, preferential methylation in HBV-related HCC was validated in 1 gene only. However, 15 genes were found methylated preferentially in HCV-related HCC, which was independent from age. Hierarchical clustering of HCC using these 15 genes stratified HCV-related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer-related signaling such as RAS/RAF/ERK and Wnt/b-catenin pathways. It was indicated that genes methylated preferentially in HCV-related HCC exist, and it was suggested that DNA methylation might play an important role in HCV-related HCC by silencing cancer-related pathway inhibitors. we analyzed aberrant promoter methylation in 6 HCC clinical samples (including 3 HBV-related HCCs and 3 HCV-related HCCs) and their matched noncancerous tissues on genome-wide scale by the method. Candidate regions of promoter methylation preferentially to HBV-related HCC and HCV-related HCC were selected, and the methylation levels of these genes were measured quantitatively using MALDI-TOF mass spectrometry. Expression levels of these 6 pairs of HCC and 4 more pairs of HCCs and surrounding noncancerous tissues were analyzed by expression array and are reported in this Series. <br><br>This experiment was reloaded in November 2010 after additional curation. this dataset is part of the TransQST collection.

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Human leukocyte antigen gene polymorphisms are associated with systemic inflammation in hepatitis B virus-related hepatocellular carcinoma.

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Human leukocyte antigen gene polymorphisms are associated with systemic inflammation in hepatitis B virus-related hepatocellular carcinoma.

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