Osiecki Rafał, Popławski Piotr, Sys Dorota, Bogusławska Joanna, Białas Alex, Zawadzki Marek, Piekiełko-Witkowska Agnieszka, Dobruch Jakub
Department of Urology, Centre of Postgraduate Medical Education, Independent Public Hospital of Prof. W. Orlowski, Warsaw, Poland.
Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Warsaw, Poland.
Clin Genitourin Cancer. 2025 Apr;23(2):102294. doi: 10.1016/j.clgc.2024.102294. Epub 2024 Dec 30.
microRNAs (miRNAs) are small noncoding RNAs and promising cancer biomarkers. Prostate-specific antigen (PSA) testing revolutionized prostate cancer (PCa) diagnostics and monitoring. However, PSA testing also contributes to PCa overdiagnoses that are detrimental on patients' health and may lead to overtreatment. Here, we searched for circulating miRNAs that could serve as biomarkers facilitating differentiation between PCa and benign prostate hyperplasia (BPH).
66 patients with PCa or BPH were investigated (33 patients in each cohort). Men with PCa underwent minimally invasive radical prostectomy (RP), whereas men with BPH underwent either holmium laser enucleation of the prostate (HOLEP), transurethral resection of the prostate (TURP) or simple prostatectomy.
We performed RNAseq of PCa and BPH serum samples, integrated our data with TCGA-PRAD cohort, followed by qPCR validation using independent cohort of PCa and BPH patients.
RNAseq detected 295 miRNAs in serum samples, including 283 miRNAs that were both expressed by PCa tissues and present in PCa sera. 10 miRNAs were selected for qPCR validation. Expression of serum miR-1-3p, miR-96-5p, miR-148a-3p, and miR-375-3p was decreased in PCa patients when compared to BPH samples. Diagnostic accuracy of combinations of PSA with geometric means of [miR-1-3p, miR-148a-3p], [miR-148a-3p, miR-375-3p], and [miR-375-3p, miR-96-5p] exceed diagnostic value of PSA alone, with the top AUC 0.97 for [miR-1-3p, miR-148a-3p]/PSA (cut-off < 0.002893, sensitivity 95.83 %, specificity 91.30 %).
In conclusion, we found a miRNAs that can support PCa diagnosis.
微小RNA（miRNA）是小型非编码RNA，有望成为癌症生物标志物。前列腺特异性抗原（PSA）检测彻底改变了前列腺癌（PCa）的诊断和监测方式。然而，PSA检测也导致了前列腺癌的过度诊断，这对患者健康有害，并可能导致过度治疗。在此，我们寻找可作为生物标志物的循环miRNA，以促进前列腺癌与良性前列腺增生（BPH）的鉴别诊断。
对66例患有PCa或BPH的患者进行了研究（每个队列33例患者）。患有PCa的男性接受了微创根治性前列腺切除术（RP），而患有BPH的男性接受了前列腺钬激光剜除术（HOLEP）、经尿道前列腺切除术（TURP）或单纯前列腺切除术。
我们对PCa和BPH血清样本进行了RNA测序，将我们的数据与TCGA-PRAD队列进行整合，随后使用PCa和BPH患者的独立队列进行qPCR验证。
RNA测序在血清样本中检测到295种miRNA，其中包括283种在PCa组织中表达且存在于PCa血清中的miRNA。选择了10种miRNA进行qPCR验证。与BPH样本相比，PCa患者血清中miR-1-3p、miR-96-5p、miR-148a-3p和miR-375-3p的表达降低。PSA与[miR-1-3p，miR-148a-3p]、[miR-148a-3p，miR-375-3p]和[miR-375-3p，miR-96-5p]几何平均值的组合诊断准确性超过单独PSA的诊断价值，但最高AUC为[miR-1-3p，miR-148a-3p]/PSA的0.97（临界值<0.002893，敏感性95.83%，特异性91.30%）。
总之，我们发现了一种可辅助前列腺癌诊断的miRNA。
