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SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer

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Item Type:Article
Title:SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer
Creators Name:Schmid, F. and Burock, S. and Klockmeier, K. and Schlag, P.M. and Stein, U.
Abstract:BACKGROUND: Colorectal cancer is one of the main cancer diseases in the Western world. About 90% of the deaths arise from formation of distant metastasis. The expression of the newly identified gene metastasis-associated in colorectal cancer 1 (MACC1) is a prognostic indicator for colon cancer metastasis. Here we analyzed for the first time of the impact of single nucleotide polymorphisms (SNPs) in the coding region of MACC1 for clinical outcome of colorectal cancer patients. Additionally, we screened met proto-oncogene (Met), the transcriptional target gene of MACC1, for mutations. METHODS: We sequenced the coding exons of MACC1 and Met in colorectal tumors and correlated the polymorphisms to clinical data, including metachronous metastasis, UICC stages, tumor invasion, lymph node metastasis and patients' survival. Furthermore, we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells. RESULTS: We identified three MACC1 SNPs: L31V in 13%, S515L in 48% and R804T in 84% of 154 tumors analyzed. We found no correlation of these SNPs to clinicopathological parameters or to patients' survival, when analyzing the entire patients' cohort. However, the MACC1 SNP S515L correlated significantly to decreased metastasis-free survival in younger colon cancer patients of early stages. In cell culture, MACC1 SNPs did not affect MACC1-induced cell motility and proliferation. CONCLUSION: In summary, the occurence of the identified coding MACC1 SNPs L31V, S515L, and R804T in primary colorectal tumors does not improve the prediction for metastasis formation or for patients' survival compared to MACC1 expression analysis alone. The MACC1 SNP S515L might be of prognostic value for younger colon cancer patients in early stages.
Keywords:Colorectal Cancer, Metastasis, MACC1, Single Nucleotide Polymorphisms
Source:Molecular Cancer
Publisher:BioMed Central
Page Range:49
Date:29 July 2012
Official Publication:https://doi.org/10.1186/1476-4598-11-49
PubMed:View item in PubMed

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