Matrix metalloproteinase gene mutations and bioinformatics of telocytes in hepatocellular carcinoma

Telocytes (TCs) have crucial functions to promote the metastasis of hepatocellular carcinoma (HCC) by over-expressing matrix metalloproteinases (MMPs), but the mechanism by which TCs secrete MMPs in the genome is still unknown. We first cultured and isolated primary TCs from distinct liver cancer tissues and hepatic hemangioma surrounding tissues (Control group). Their whole exon genes were tested by Illumina HiSeq family of platforms and by high-throughput sequencing as well as variant mutations. Moreover, immunohistochemistry, Western blot, and quantitative reverse transcription-polymerase chain reaction assays were utilized to assess the expression of MMPs. The perniciousness of signal-nucleotide polymorphism (SNP) mutations of proteins were predicted by the Polyphen-2 database. Divergent expression and overall survival (OS) of MMPs was screened by StarBase-Pan Cancer plate; and MMPs associated signaling pathways were found by Kyoto Encyclopedia Genes and Genomes. The competing endogenous RNA (ceRNA) network was constructed by Cytoscape software. We found that 12 specific types of SNP mutations related to 5 types of MMPs occurred in TCs of liver malignant tumors as a potential result of MMP1, MMP9, and MMP17 overexpression. High levels of MMP1, MMP7, and MMP9 represented poor OS in HCC, and an interactive network of MMPs is shown. Allele shifts of C/T (rs20544) and G/C (rs2250889) in MMP9 were risk factors for TCs in HCC by the prediction of the Polyphen-2 Database. (MMP9 (-3 C/T)) mutation might be a genetic mechanism of upregulating MMP9 in TCs.

Automated summary

Telocytes play a crucial role in promoting the metastasis of hepatocellular carcinoma (HCC) by overexpressing matrix metalloproteinases (MMPs), but the mechanism of MMP secretion in TCs remains unknown. In this study, TCs were cultured from liver cancer tissues and surrounding tissues. SNP mutations related to MMPs were identified, and high levels of MMP1, MMP7, and MMP9 were associated with poor overall survival in HCC. These findings suggest that TCs may contribute to the development of HCC by regulating an interactive network of MMPs.