A complex microsatellite at chromosome 7q33 as a new prognostic marker of colorectal cancer

Abstract

Disease-specific markers are critical for early diagnosis, targeted therapy and prognostic prediction of diseases. Current study reports a complex microsatellite as a new prognostic marker of sporadic colorectal cancer. This microsatellite located at Chromosome 7q33 is composed of three tetranucleotide tandem repeats, (TTCC)₂(TCCC)₅(TCCT)₇, flanked by a CT-rich sequence. We analyzed polymorphisms of this microsatellite in 158 sporadic colorectal cancer, 143 matched normal adjacent tissues (NAT) and 150 health donors. Our results showed that this complex microsatellite was instable with polymorphic frequency of 77.2% in colorectal cancer, 52.4% in NAT and 54.7% in health donors (p<0.01) when compared to reference sequence. In the three tandem repeats, (TCCT)₇ site was most polymorphic accounting for over 70.0% of polymorphisms in this complex microsatellite, followed by (TTCC)₂ site for approximately 20%. Polymorphisms in (TCCC)₅ was rare. Polymorphisms at the (TCCT)₇ site were mainly insertions of 1 to 4 copies of TCCT (88.6%), and deletions occurred in about 6.4% of cases. The (TTCC)₂ site was featured with one copy TTCC insertions. Pair-wise analyses between colorectal tumors and NAT revealed that 88 of 121 (72.7%) tumors displayed expansion, contraction or both in these tetranucleotide tandem repeats when compared to NAT. A cross-analysis with clinicopathological data of 158 colorectal cancers revealed that polymorphic alterations of the microsatellite associated with less lymphatic metastasis (p<0.001), and the colorectal cancer patients with polymorphic changes in this microsatellite demonstrated better survival (n=112, p=0.0058). Together these data suggest that this complex microsatellite is a potential prognostic marker of sporadic colorectal cancer.