Single nucleotide polymorphisms in the metastasis-associated in colon cancer-1 gene predict the recurrence of hepatocellular carcinoma after transplantation.
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.
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Zhiyun
Z
Zheng
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Sheng
S
Gao
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China. ; 2. Division of Hepatobiliary and Pancreatic surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Zhe
Z
Yang
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Haiyang
H
Xie
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Cheng
C
Zhang
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Bingyi
B
Lin
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China. ; 2. Division of Hepatobiliary and Pancreatic surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Liming
L
Wu
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China. ; 2. Division of Hepatobiliary and Pancreatic surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Shusen
S
Zheng
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China. ; 2. Division of Hepatobiliary and Pancreatic surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
Lin
L
Zhou
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
C544162:MACC1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors
epithelial-to-mesenchymal transition; metastasis-associated in colon cancer-1