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

Molecular Cancer

Research

Susen Burock¹  Peter M Schlag²  Konrad Klockmeier³  Felicitas Schmid⁴  Ulrike Stein⁵ 

[1] Charité Comprehensive Cancer Center, Berlin, Invalidenstraße 80, 10117, Berlin, Germany;Charité Comprehensive Cancer Center, Berlin, Invalidenstraße 80, 10117, Berlin, Germany;a joint cooperation between the Charité Medical Faculty and the Max-Delbrück-Center for Molecular Medicine, Experimental and Clinical Research Center, Robert-Rössle-Straße 10, 13125, Berlin, Germany;Free University Berlin, Kaiserswerther Str. 16-18, 14195, Berlin, Germany;Max-Delbrück-Center for Molecular Medicine, Berlin, Robert-Rössle-Straße 10, 13125, Berlin, Germany;a joint cooperation between the Charité Medical Faculty and the Max-Delbrück-Center for Molecular Medicine, Experimental and Clinical Research Center, Robert-Rössle-Straße 10, 13125, Berlin, Germany;

关键词: Colorectal cancer;    Metastasis;    MACC1;    Single nucleotide polymorphisms;   

DOI  :  10.1186/1476-4598-11-49

 received in 2011-11-28, accepted in 2012-07-13,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundColorectal cancer is one of the main cancers 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 colon cancer 1 (MACC1) is a prognostic indicator for colon cancer metastasis. Here, we analyzed for the first time 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.MethodsWe sequenced the coding exons of MACC1 in 154 colorectal tumors (stages I, II and III) and the crucial exons of Met in 60 colorectal tumors (stages I, II and III). We analyzed the association of MACC1 polymorphisms with clinical data, including metachronous metastasis, UICC stages, tumor invasion, lymph node metastasis and patients’ survival (n = 154, stages I, II and III). Furthermore, we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells.ResultsWe genotyped three MACC1 SNPs in the coding region. Thirteen % of the tumors had the genotype cg (rs4721888, L31V), 48% a ct genotype (rs975263, S515L) and 84% a gc or cc genotype (rs3735615, R804T). We found no association of these SNPs with clinicopathological parameters or with patients’ survival, when analyzing the entire patients’ cohort. An increased risk for a shorter metastasis-free survival of patients with a ct genotype (rs975263) was observed in younger colon cancer patients with stage I or II (P = 0.041, n = 18). In cell culture, MACC1 SNPs did not affect MACC1-induced cell motility and proliferation.ConclusionIn summary, the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients’ survival compared to MACC1 expression analysis alone. The ct genotype (rs975263) might be associated with a reduced survival for younger colon cancer patients in early stages. However, further studies with larger sample sizes are needed.

【 授权许可】

Unknown   
© Schmid et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.