Oncotarget

Research Papers:

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

Xu Ye, Hongyu Deng, Min Su, Qianjin Liao, Dan Huang, Duan-Fang Liao, Zhi-Qiang Xiao and Deliang Cao _

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Oncotarget. 2017; 8:88760-88769. https://doi.org/10.18632/oncotarget.21077

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Abstract

Xu Ye1,2,3, Hongyu Deng3, Min Su3, Qianjin Liao3, Dan Huang4, Duan-Fang Liao4, Zhi-Qiang Xiao1,2 and Deliang Cao3,4

1Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China

2The Higher Educational Key Laboratory For Cancer Proteomics and Translational Medicine of Hunan province, Xiangya Hospital, Central South University, Changsha, Hunan 410005, China

3Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China

4Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China

Correspondence to:

Deliang Cao, email: dlcao1998@gmail.com

Zhi-Qiang Xiao, email: zqxiao2001@hotmail.com

Keywords: colorectal cancer, microsatellite, polymorphisms, survival, prognostic marker

Received: April 18, 2017     Accepted: June 28, 2017     Published: September 16, 2017

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.


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