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Prospective Study of CRMP4 Promoter Methylation in Prostate Biopsies as a Predictor For Lymph Node Metastases

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机构: [1]Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [2]Department of Pathology ,The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [3]Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [4]Department of Urology, St. Elisabeth Hospital, University of Leipzig, Leipzig, Germany [5]Department of Urology, The First Affiliated Hospital, Nanchang University, Nanchang, China [6]Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai, China [7]Department of Urology, Cancer Center, Sun Yat-sen University, Guangzhou, China [8]Department of Urology, Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, Guangzhou, China [9]Department of Urology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China [10]Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China [11]Department of Urology, Cancer Hospital,Guangxi Medical University, Nanning, China [12]Department of Urology, Guangdong General Hospital, Guangzhou, China [13]Department of Urology, Shenzhen People’s Hospital, Shenzhen, China [14]Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China
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Background: For patients with prostate cancer (PCa), the presence of pelvic lymph node metastasis (LNM) is a strong predictor of poor outcome. However, the approaches with promising sensitivity and specificity to detect LNM are still lacking. We investigated the value of collapsin response mediator protein 4 (CRMP4) promoter methylation in biopsies as a predictor for LNM. Methods: CRMP4 promoter methylation at two previously identified CpG sites was determined in 80 case-matched biopsy samples (the training set) using bisulfite pyrosequencing. The predictive cutoff value was independently validated using cohort I of 339 PCa patients (Southern China) and cohort II of 328 case patients (Germany, across China). Mann-Whitney U test, the receiver operating characteristic curve, McNemar's test, and logistic regression were used to assess data. All statistical tests were two-sided. Results: In the training set, CRMP4 promoter methylation (>= 15.0% methylated) was statistically significantly associated with LNM (P < .001). Successful validations were achieved in both cohorts I and II (sensitivity = 92.3%, 95% confidence interval [CI] = 79.3 to 97.9, and sensitivity = 92.2%, 95% CI = 81.1 to 97.8, respectively; specificity = 92.7%, 95% CI = 80.2 to 99.1, and specificity = 91.3%, 95% CI = 87.4 to 94.4, respectively). The sensitivity of CRMP4 promoter methylation is superior to conventional MRI (cohort I: 92.3% vs 26.2%, P < .001; cohort II: 92.2% vs 33.3%, P<. 001). CRMP4 promoter methylation is an independent predictor of LNM (cohort I: hazard ratio [HR] = 8.35, 95% CI = 5.64 to 12.35, P < .001; cohort II: HR = 12.46, 95% CI = 5.82 to 26.70, P < .001) in a multivariable analysis model. Conclusion: CRMP4 promoter methylation in diagnostic biopsies could be a robust biomarker for LNM in PCa.

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出版当年[2017]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
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第一作者机构: [1]Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [*1]Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
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通讯机构: [1]Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China [*1]Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
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