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Background   The presence of a capsule is an important prognostic factor in hepatocellular carcinoma (HCC). Capsule formation is affected by tumor-host interaction, which may include collagen deposition and extracellular matrix (ECM) degradation.Purpose   This study aimed to examine whether single-nucleotide polymorphisms (SNPs) in the genes for COL1A1 MUC15, MMP14, CD97, SMYD3, BRAF, and transforming growth factor beta 1 (TGF- β ) are related to capsule formation.Methods   We prospectively recruited and analyzed 185 patients with HCC with or without a capsule between 2019 and 2020. The SNPs involved were analyzed by polymerase chain reaction. Differences in the allele and genotype frequency between the cases and controls were evaluated using the chi-square test. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis with adjustment for age and sex. Stratification analyses were also performed with preselected variables.Results   The single-locus analysis showed that the presence of a capsule was significantly associated with five SNPs : MUC15 rs17309195 ( P =0.01), rs12271124 ( P = 0.02), rs10430847 ( P =0.04), MMP14 rs17884816 ( P =0.01), and BRAF rs74512895 ( P =0.03). Adjusted logistic regression revealed that the decreased capsule formation was statistically significantly associated with BRAF rs76603725, COL1A1 rs2269336, and MUC15 rs17309195, while MMP14 rs17884816 and MUC15 rs10430847, rs2063278, and rs967490 were associated with increased capsule formation. The MUC15 block 2 haplotype was associated with increased capsule formation.Conclusions   MUC15, MMP14, BRAF, and COL1A1 gene polymorphisms are associated with capsule formation in HCC. Studies involving larger samples are needed to confirm our results.

Gene Polymorphism of MUC15, MMP14, BRAF, and COL1A1 Is Associated with Capsule Formation in Hepatocellular Carcinoma