Single Nucleotide Polymorphisms in the Metastasis-associated in Colon Cancer-1 Gene Predict the Recurrence of Hepatocellular Carcinoma after Transplantation

Abstract

Background: The newly identified metastasis-associated in colon cancer-1 (MACC1) gene is involved in angiogenesis, epithelial-to-mesenchymal transition (EMT), invasiveness, and metastasis in a variety of malignancies. Overexpression of MACC1 gene is a prognostic marker for poor outcome of hepatocellular carcinoma (HCC) patients. However, the association between genetic polymorphisms of MACC1 gene and poor outcome in HCC has been not been performed. We therefore investigated the correlation of MACC1 single nucleotide polymorphisms (SNPs) with tumor recurrence and overall survival in HCC patients undergoing liver transplantation (LT). Methods: The study included 187 HCC patients treated with LT. Five polymorphisms in the MACC1 gene (rs1990172, rs3735615, rs4721888, rs2241056, rs975263) were genotyped in 183 cases of tumorous tissue sample and 117 cases of adjacent normal tissue sample using SNaP-Shot assays. The association of SNPs with tumor recurrence and overall survival was then analyzed by additive, dominant, recessive, and overdominant models in a cohort of 156 HCC patients. Results: In terms of tumor recurrence, heterozygous of SNP rs1990172 and SNP rs975263 showed a significant high risk of relapse using univariate and multivariate analysis (overdominant, HR(95%CI)=2.27 [1.41-3.66], P=0.001; HR(95%CI)=2.16 [1.37-3.39], P=0.001). But the difference between heterozygous of these two SNPs and overall survival did not reach a significance in all models. The other three investigated SNPs were not significantly associated with tumor recurrence and overall survival (P>0.05). In addition, we found no significant difference in genotype frequencies between HCC and controls. Conclusions: Our data suggest that SNP rs1990172 and SNP rs975263 in the MACC1 gene may be potential genetic markers for HCC recurrence in LT patients.

Investigation of metastasis-associated in colon cancer-1 genetic variants in the development and clinicopathologcial characteristics of uterine cervical cancer in Taiwanese women

“…Meanwhile, both rs1990172 (A29858C) and rs3095009 (C77360T) are not in coding exon but in intron regions, which exhibit no impact on coding exon of MACC1 gene [13,18]. Moreover, Zheng et al found no significant difference in the allele or genotype distribution of the MACC1 SNPs between hepatocellular carcinoma (HCC) tissues and adjacent normal tissues, which showed that MACC1 SNPs probably have no influence on the risk of development of HCC [35].…”

Metastasis-associated in colon cancer-1 and aldehyde dehydrogenase 1 are metastatic and prognostic biomarker for non-small cell lung cancer

“…It is also involved in angiogenesis and lymphangiogenesis to promote tumor invasion and metastasis [43, 44]. In turn, these microvessels and microlymphantic vessels sustain CSCs that further promote tumor invasion and metastasis, thus creating a positive cycle of tumor advancement.…”

The expression of metastasis-associated in colon cancer-1 and KAI1 in gastric adenocarcinoma and their clinical significance

“…Meanwhile, MACC1 could be bound to the promoter of the MET gene and activate the HGF/MET signaling pathway to promote cancer cell proliferation, invasion, and metastasis [3, 4]. Furthermore, it could promote angiogenesis and lymphangiogenesis to lead to cancer cell invasion and metastasis [40, 41]. Moreover, KAI1 is able to be bind to c-MET to form a complex or quench the activation of HGF, thus preventing the activation of MACC1 to inhibit the migration of tumor cells [42, 43].…”