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| 血浆微RNA联合检测在前列腺癌中的诊断价值 |
| 蔡鹏1,吴叶晨2,陈曦1,张益萍2,马少泽2,朱小琼3,胡锦新2,殷建华1*,曹廷虎2* |
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(1. 海军军医大学(第二军医大学)海军医学系海军流行病学教研室, 上海 200433;
2. 上海市宝山区中西医结合医院泌尿外科, 上海 201900;
3. 安徽医科大学公共卫生学院营养与食品卫生学系, 合肥 230032
*通信作者) |
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| 摘要: |
| 目的 分析前列腺癌患者血浆miRNA的差异表达，探索血浆miRNA联合检测在前列腺癌中的诊断潜能。方法 应用基因表达汇编数据库获得前列腺癌患者血浆及血清差异表达的miRNA，通过最近邻中心分类器曲线下面积优化模型（NCC-AUC）筛选出3个权重最高的miRNA；收集上海市宝山区中西医结合医院诊治的45例前列腺癌患者（前列腺癌组）、40例慢性前列腺炎患者（前列腺炎组）和42例健康体检者（健康对照组）血浆样本，采用qPCR对候选血浆miRNA表达水平进行检测；应用ROC曲线分析候选miRNA单独及联合检测对前列腺癌的诊断价值。结果 通过生物信息学分析，获得26个前列腺癌相关的差异表达miRNA，经NCC-AUC进一步筛选，miRNA-21-5p、miRNA-5189-5p和miRNA-6780a-5p权重最高，进入临床样本验证阶段。临床验证结果显示，血浆miRNA-21-5p水平在健康对照组、前列腺炎组、前列腺癌组中依次升高，3组之间差异有统计学意义（P<0.01）；前列腺炎组血浆miRNA-5189-5p水平低于前列腺癌组与健康对照组（P均<0.01）；前列腺癌组血浆miRNA-6780a-5p水平高于前列腺炎组和健康对照组（P均<0.01）。ROC曲线分析显示，血浆miRNA-21-5p和miRNA-6780a-5p对前列腺癌均有较好的诊断潜能（P均<0.001），AUC分别为0.695和0.787，灵敏度分别为95.6%和64.4%，特异度分别为41.5%和81.7%。miRNA-21-5p与miRNA-6780a-5p联合应用可有效提高对前列腺癌的诊断效能，AUC为0.830，灵敏度和特异度分别为82.2%和74.4%。结论 血浆miRNA-21-5p和miRNA-6780a-5p均有成为前列腺癌诊断标志物的潜能，两者联合检测可提高对前列腺癌的诊断效能。 |
| 关键词: 前列腺肿瘤 微RNA-21-5p 微RNA-5189-5p 微RNA-6780a-5p 诊断 |
| DOI：10.16781/j.CN31-2187/R.20220673 |
| 投稿时间：2022-08-18修订日期：2022-09-23 |
| 基金项目:上海市宝山区科学技术委员会科技创新专项（19-E-41）. |
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| Diagnostic value of combined detection of plasma microRNAs for prostate cancer |
| CAI Peng1,WU Ye-chen2,CHEN Xi1,ZHANG Yi-ping2,MA Shao-ze2,ZHU Xiao-qiong3,HU Jin-xin2,YIN Jian-hua1*,CAO Ting-hu2* |
(1. Department of Navy Epidemiology, Faculty of Naval Medicine, Naval Medical University (Second Military Medical University), Shanghai 200433, China;
2. Department of Urology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai 201900, China;
3. Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China
*Corresponding author) |
| Abstract: |
| Objective To analyze the differential expression levels of plasma microRNAs (miRNAs) in prostate cancer patients, and to investigate the potential of combined plasma miRNA detection in the diagnosis of prostate cancer. Methods The Gene Expression Omnibus database was used to screen out the differentially expressed miRNAs in prostate cancer plasma or serum, and 3 miRNAs with the highest weights were screened out by using nearest centroid classifier for area under curve optimization (NCC-AUC) method. A total of 45 plasma samples from patients with prostate cancer (prostate cancer group), 40 from patients with chronic prostatitis (prostatitis group) and 42 from healthy physical examination participants (healthy control group) were collected from Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine. The expression levels of candidate plasma miRNAs were verified by quantitative polymerase chain reaction. The diagnostic value of candidate miRNAs and combined miRNAs for prostate cancer was analyzed by receiver operating characteristic (ROC) curve. Results A total of 26 differentially expressed miRNAs related to prostate cancer were obtained by bioinformatics analysis, and 3 miRNAs (miRNA-21-5p, miRNA-5189-5p, and miRNA-6780a-5p) with the highest weights in NCC-AUC mode were included for the clinical validation stage. Clinical verification results showed that the expression level of plasma miRNA-21-5p was increased successively in the healthy control group, prostatitis group and prostate cancer group, and the differences between the 3 groups were statistically significant (P<0.01). The expression level of plasma miRNA-5189-5p in the prostatitis group was significantly lower than that in the prostate cancer group and healthy control group (both P<0.01). The expression level of plasma miRNA-6780a-5p in the prostate cancer group was significantly higher than that in the prostatitis group and healthy control group (both P<0.01). ROC curve showed that both plasma miRNA-21-5p and miRNA-6780a-5p had excellent diagnostic potential for prostate cancer (both P<0.001); the values of area under curve (AUC) were 0.695 and 0.787, sensitivities were 95.6% and 64.4%, and specificities were 41.5% and 81.7%, respectively. The combination of miRNA-21-5p and miRNA-6780a-5p could improve the diagnostic efficiency, with an AUC of 0.830, a sensitivity of 82.2%, and a specificity of 74.4%. Conclusion Plasma miRNA-21-5p and miRNA-6780a-5p are both potential diagnostic markers for prostate cancer, and the combined detection of both can improve the diagnostic efficacy. |
| Key words: prostatic neoplasms microRNA-21-5p microRNA-5189-5p microRNA-6780a-5p diagnosis |
