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

Abstract

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.

An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte–tumor cell crosstalk, local immunosuppression and tumor progression

“…Macroscopic and pathological examinations revealed that a capsule existed around the tumors in 10%–76% of the HCC patients, but the tumor capsule rarely existed in the ICC patients. 58 , 59 It is believed that the formation of this fibrous capsule results from tumor–host interactions, and that the capsule acts as a physical barrier, preventing the infiltration of immune cells in the margin area, hindering the interplay among the cells around the border. 58 , 60 Thus, we only selected liver cancer patients who lacked a complete tumor capsule upon pathological examination to permit better characterization of the invasive zone.…”

A novel diagnostic four-gene signature for hepatocellular carcinoma based on artificial neural network: Development, validation, and drug screening

“…Vemurafenib was also noticed to be the substrate of SLCO1B3, which might influence the absorption and elimination of the HCC chemotherapy drug (23340295). Nevertheless, BRAF gene polymorphisms were associated with capsule formation in HCC ( Sun et al, 2021 ). BRAF-mutation-mediated MAPK pathway downstream was often constitutively activated and led to cancer cell differentiation, proliferation, angiogenesis, and anti-apoptosis, suggesting targeting the BRAF pathway might inhibit HCC progression in the future ( Gnoni et al, 2019 ).…”

Associations Between Single Nucleotide Polymorphisms of Hypoxia-Related Genes and Capsule Formation in Hepatocellular Carcinoma

“…The genomic DNA extracted from peripheral blood samples was used as the template for polymerase chain reaction (PCR), and PCR assays were performed as previously described. 13 Three primers were designed for each SNP, two for PCR amplification of approximately 120 bp product adjacent to the SNP site and one for single base extension. SNP genotypes were determined by analyzing primer extension products on mass spectrometry.…”

“… 12 Our previous study revealed a correlation between polymorphisms in several genes and the formation of tumor capsule. 13 …”