ABSTRACT
ObjectiveTo investigate the expression of TM6SF2 in hepatocellular carcinoma (HCC) tissue and its biological functions by data mining in tumor databases. MethodsThe GEPIA database was applied to measure the change in the mRNA expression level of TM6SF2 in HCC tissue, and OncoLnc was used to analyze the association of TM6SF2 expression with the survival time of HCC patients. The cBioPortal and LinkedOmics databases were used to analyze the genes associated with the expression of TM6SF2 in HCC tissue, and the DAVID6.8 and STRING databases were used to perform a bioinformatics analysis of TM6SF2 and the genes associated with its expression. The t-test was used to investigate the difference in the mRNA expression of TM6SF2 between HCC tissue and adjacent tissue. The Spearman correlation coefficient was used to analyze the correlation of gene expression. The Kaplan-Meier method was used to calculate survival percentage, and the log-rank test was used to analyze the difference in survival percentage. ResultsCompared with the normal liver tissue, the HCC tissue had low mRNA expression of TM6SF2 (｜log2FC｜cut-off = 0.5, P＜0.01). Compared with those with high expression of TM6SF2, the patients with low expression had a significant reduction in overall survival time (χ2=9.897，P＜0.01). Data analysis showed that a total of 49 genes were associated with the expression of TM6SF2 in HCC tissue, and the gene ontology analysis showed that these genes were enriched in the biological processes and functions including fatty acid synthesis, fatty acid ligase activation, and thrombin regulation (P＜0.05). The Kyoto Encyclopedia of Genes and Genome pathway analysis showed that these genes were mainly involved in the signaling pathways of alanine metabolism, peroxisome proliferator-activated receptor signaling pathway, and bile secretion (P＜0.05). The protein-protein interaction network analysis showed that the genes of SERPINC1, NR1I2, SERPINA10, and SLC10A1 had marked or potential interaction with TM6SF2 (P＜0.01). ConclusionTumor data mining can quickly obtain the information on the expression of TM6SF2 in HCC tissue and provide a bioinformatics basis for exploring the role of TM6SF2 in the development and progression of HCC.
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Objective To explore the SNP effects ofpatatin-like phospholipase domain which containing 3 (PNPLA3),transmembrane 6 superfamily member 2 (TM6SF2) gene,environmental effects of smoking,alcohol drinking and interaction between gene-gene,gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC).Methods We collected anticoagulant peripheral blood from patients of HBV-HCC,chronic hepatitis B (CHB),liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926,using the flight mass spectrometry method.The optimal assignment value of gene polymorphisms was defined by using the online SNP stats.Hardy-Weinberg (H-W) balance was tested for SNP.Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method.The gene-gene,gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods.Results The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (x2=11.980,P＜0.005).Two loci frequency distributions in the other groups were all in accordandce with the H-W balance.After adjusting for influences on age and sex and comparing to the healthy group,the rs58542926 mutation appeared as OR=1.659,95％CI:1.026-2.684,P=0.039,in the HBV-HCC group.When comparing to CHB group,the HBV-HCC group presented that drinking as OR=1.680,95％CI:1.121-2.519,P=0.012.When comparing to the LC group,the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively,in the HBV-HCC group.When comparing to the CHB + LC group,interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885,P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965,P=0.024).As for drinking and mutation of rs738409,the multiplication model of logistic regression showed no statistically significant differences.Interaction between smoking and drinking appeared as OR=1.756 (P＜0.001) in the logistics regression multiplication model.Conclusions Factors as mutation of TM6SF2,smoking and drinking all appeared as risk factors for HBV-HCC.Mutations of both PNPLA3 and TM6SF2,together with smoking and drinking all served as risk factors for HBV-HCC.However,the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
ABSTRACT
Objective To explore the SNP effects ofpatatin-like phospholipase domain which containing 3 (PNPLA3),transmembrane 6 superfamily member 2 (TM6SF2) gene,environmental effects of smoking,alcohol drinking and interaction between gene-gene,gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC).Methods We collected anticoagulant peripheral blood from patients of HBV-HCC,chronic hepatitis B (CHB),liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926,using the flight mass spectrometry method.The optimal assignment value of gene polymorphisms was defined by using the online SNP stats.Hardy-Weinberg (H-W) balance was tested for SNP.Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method.The gene-gene,gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods.Results The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (x2=11.980,P＜0.005).Two loci frequency distributions in the other groups were all in accordandce with the H-W balance.After adjusting for influences on age and sex and comparing to the healthy group,the rs58542926 mutation appeared as OR=1.659,95％CI:1.026-2.684,P=0.039,in the HBV-HCC group.When comparing to CHB group,the HBV-HCC group presented that drinking as OR=1.680,95％CI:1.121-2.519,P=0.012.When comparing to the LC group,the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively,in the HBV-HCC group.When comparing to the CHB + LC group,interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885,P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965,P=0.024).As for drinking and mutation of rs738409,the multiplication model of logistic regression showed no statistically significant differences.Interaction between smoking and drinking appeared as OR=1.756 (P＜0.001) in the logistics regression multiplication model.Conclusions Factors as mutation of TM6SF2,smoking and drinking all appeared as risk factors for HBV-HCC.Mutations of both PNPLA3 and TM6SF2,together with smoking and drinking all served as risk factors for HBV-HCC.However,the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC.
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BACKGROUND/AIMS: It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. METHODS: The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. RESULTS: The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. CONCLUSIONS: In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.