Jingyu Wang1, Wenfeng Li2, Yuqi Wang3, Chen Li4, Meiman Ding5, Honghe Zhang6, Maode Lai7. 1. Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China; Department of Pathology, the First Hospital of Jiaxing, Zhejiang, PR China. Electronic address: 11018140@zju.edu.cn. 2. Department of Chemoradiotherapy, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang, PR China. Electronic address: lwf720325@medmail.com.cn. 3. Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: 1026643390@qq.com. 4. Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: keaidelichen@163.com. 5. The Criminal Investigation Detachment of Jiaxing Public Security Bureau, Zhejiang, PR China. Electronic address: 526983038@qq.com. 6. Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: honghezhang@zju.edu.cn. 7. Department of Pathology, School of Medicine, Zhejiang University, Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang, PR China. Electronic address: lmp@zju.edu.cn.
Abstract
BACKGROUND: Growth differentiation factor 15 (GDF15) plays important roles in the carcinogenesis of many types of tumors. The aim of this study was to investigate whether H6D polymorphism is contributed to the genesis, progress and prognosis of colorectal cancer (CRC) in Chinese population. METHODS: Pyrosequencing was used to determine the H6D genotypes. The relationship between the genotypes and clinical characteristics was analyzed. RESULTS: The frequency of CG+GG genotype in the GDF15 H6D polymorphism was significantly increased in CRC patients when compared with controls [odds ratio (OR), 1.543; 95% confidence interval (95% CI), 1.138-2.094, P=0.005]. We also found that the patients with CG+GG genotype had an increased risk of death from colon cancer than those carrying homozygote CC [hazard ratio (HR), 2.472; 95% CI, 1.172-5.214; P=0.017] and the patients with CG+GG genotype of colon cancer also have a positive correlation with distant metastasis than those carrying homozygote CC (χ(2)=4.087, P=0.043). For the first time, H6D was also identified as somatic mutation when compared the H6D genotype in tumor tissues and their matched normal tissues, and the mutation rate is 7.2%. The male CRC patients with the H6D mutation were susceptible to distant metastasis (P=0.028, χ(2)=4.820) and had a relatively poor prognosis. CONCLUSION: Our results suggest that the H6D genetic variant may be considered as a biomarker of tumorgenesis, metastasis and prognosis in colorectal cancer in Chinese population.
BACKGROUND:Growth differentiation factor 15 (GDF15) plays important roles in the carcinogenesis of many types of tumors. The aim of this study was to investigate whether H6D polymorphism is contributed to the genesis, progress and prognosis of colorectal cancer (CRC) in Chinese population. METHODS: Pyrosequencing was used to determine the H6D genotypes. The relationship between the genotypes and clinical characteristics was analyzed. RESULTS: The frequency of CG+GG genotype in the GDF15 H6D polymorphism was significantly increased in CRCpatients when compared with controls [odds ratio (OR), 1.543; 95% confidence interval (95% CI), 1.138-2.094, P=0.005]. We also found that the patients with CG+GG genotype had an increased risk of death from colon cancer than those carrying homozygote CC [hazard ratio (HR), 2.472; 95% CI, 1.172-5.214; P=0.017] and the patients with CG+GG genotype of colon cancer also have a positive correlation with distant metastasis than those carrying homozygote CC (χ(2)=4.087, P=0.043). For the first time, H6D was also identified as somatic mutation when compared the H6D genotype in tumor tissues and their matched normal tissues, and the mutation rate is 7.2%. The male CRCpatients with the H6D mutation were susceptible to distant metastasis (P=0.028, χ(2)=4.820) and had a relatively poor prognosis. CONCLUSION: Our results suggest that the H6D genetic variant may be considered as a biomarker of tumorgenesis, metastasis and prognosis in colorectal cancer in Chinese population.