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Circulating microRNAs combined with PSA for accurate and non-invasive prostate cancer detection

医学 前列腺癌 肿瘤科 逻辑回归 前列腺特异性抗原 队列 内科学 生物标志物 前列腺 癌症 生物化学 化学
作者
Maurizia Mello‐Grand,Ilaria Gregnanin,Lidia Sacchetto,Paola Ostano,Andrea Zitella,Giulia Bottoni,Marco Oderda,Giancarlo Marra,Stefania Munegato,Barbara Pardini,Alessio Naccarati,Mauro Gasparini,Paolo Gontero,Giovanna Chiorino
出处
期刊:Carcinogenesis [Oxford University Press]
卷期号:40 (2): 246-253 被引量:31
标识
DOI:10.1093/carcin/bgy167
摘要

The dosage of prostate-specific antigen (PSA), an easily evaluable and non-invasive biomarker, has made early detection of prostate cancer (PCa) possible. However, it leads to high percentages of unnecessary biopsies and may miss aggressive tumors in men with PSA levels below 4 ng/ml. Therefore, we propose to combine circulating microRNAs (miRs) with PSA, to improve the diagnostic route for PCa. Plasma miR profiling identified candidate diagnostic miRs in a discovery cohort of 60 tumors and 60 controls (men with benign prostatic hyperplasia or healthy donors). Linear models with an empirical Bayesian approach and multivariate penalized logistic regression were applied to select tumor-associated miRs and/or clinical variables. A classifier was developed and tested on a validation cohort of 68 tumors and 174 controls consecutively collected, where miRs were evaluated by quantitative real-time polymerase chain reaction. A classifier based on miR-103a-3p, let-7a-5p and PSA could detect both overall and clinically significant tumors better than PSA alone, even in 50-69 years aged men with PSA ≤ 4 ng/ml. Even in the validation cohort, the classifier performed better than PSA alone in terms of specificity and positive predictive value, allowing to correctly identify eight out of nine tumors undetected by PSA, including three high-risk and three tumors in 50-69 years old men. Of carriers of non-malignant lesions with PSA in the 4-16 ng/ml interval, who may avoid unnecessary biopsies, 34% were correctly identified. Coupling two circulating miRs with PSA could be a useful strategy to diagnose clinically significant PCa and avoid an important fraction of unnecessary biopsies.
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