Abstract
BackgroundThe newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Deregulation of HGF/MET signaling is reported as a prognostic marker for tumorigenesis, early stage invasion, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients.MethodsThe study included 318 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032), capturing most of the common variants of the MACC1 locus, were genotyped by SNaPshot assays.ResultsOver a mean follow up period of 5.3 (± 1.0) years, 94 deaths were recorded. Carriers of the G-allele of SNP rs1990172 showed a significantly decreased overall survival (additive HR = 1.38 [1.05-1.82]; p = 0.023). Multivariate analysis adjusted for age and UICC tumor stage confirmed this result (HR = 1.49 [1.12-1.98]; p = 0.007). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (p-values > 0.05).ConclusionsFor the first time, our study investigated the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.
Highlights
The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the hepatocyte growth factor (HGF)/MET pathway
Subsequent studies have shown that overexpression of MACC1 is associated with poor disease-free survival in patients with gastric carcinoma [5] and lung adenocarcinoma [6], respectively, and it was found that MACC1 is more frequently expressed in vascular invasive hepatocellular carcinoma [7]
Age at cancer diagnosis and UICC stage were significantly associated with overall survival
Summary
The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGF/MET pathway. Subsequent studies have shown that overexpression of MACC1 is associated with poor disease-free survival in patients with gastric carcinoma [5] and lung adenocarcinoma [6], respectively, and it was found that MACC1 is more frequently expressed in vascular invasive hepatocellular carcinoma [7]. These findings suggest that MACC1 may serve as a new parameter for the prognostic prediction of different kinds of cancer
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