Manoj Anveshika, Ahmad Mohammad K, Prasad Gautam, Kumar Durgesh, Mahdi Abbas A, Kumar Manoj
Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India.
Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India.
Prostate Int. 2023 Sep;11(3):150-158. doi: 10.1016/j.prnil.2023.06.002. Epub 2023 Jun 21.
Owing to the heterogeneous nature of prostate cancer (PCa) and errors in the characterization of the disease, researchers have been trying to unveil molecular biomarkers like microRNA (miRNA) as diagnostic markers. The purpose of our study is to demonstrate the precision of a panel of miRNAs as biomarkers with diagnostic potential for risk stratification.
The present study demonstrates the comparative expression profiles of miRNA-141,-1290,-100, and -335 in both tissue and serum, including Benign Prostate Hyperplasia (BPH) and PCa, with healthy volunteers. Firstly, we demonstrate the expression of all miRNAs in the discovery cohort, including metastasis and benign tissue, and later validate their non-invasive diagnostic potential in BPH and PCa with healthy volunteers. MiRNA was isolated from tissue and serum to be quantified by RT-PCR and analyzed for biomarker potential by receiver operating characteristic (ROC) curve analysis, followed by targetome analysis of each miRNA.
Among the non-invasive miRNA assessed, it was seen that miRNA 141 ( = 0.0003) and miRNA 1290 ( < 0.0001) are oncogenic with significantly higher expression, while miRNA 100 ( = 0.0002) and miRNA 335 are tumor suppressor, in PCa as compared to controls. While for BPH, miRNA 141 ( = 0.003) and miRNA 335 ( = 0.0002) were found to be significantly oncogenic and tumor suppressors, respectively. The analysis of the ROC curve of panel miRNAs (miRNA-141,-1290, and -100) portrayed a significant area under the curve with greater sensitivity and specificity. Moreover, in-silico prediction of their respective targetomes represents their extensive involvement in PCa progression and various other cascades that aid in PCa networks.
To the best of our knowledge, we are going to report for the first time this panel of miRNA that can be used to accurately and efficiently diagnose BPH and PCa patients from healthy males.
由于前列腺癌(PCa)的异质性以及该疾病特征描述中的误差,研究人员一直在尝试揭示诸如微小RNA(miRNA)等分子生物标志物作为诊断标志物。我们研究的目的是证明一组miRNA作为具有风险分层诊断潜力的生物标志物的准确性。
本研究展示了miRNA - 141、- 1290、- 100和- 335在组织和血清中的比较表达谱,包括良性前列腺增生(BPH)、PCa以及健康志愿者。首先,我们在发现队列中展示所有miRNA的表达,包括转移组织和良性组织,随后在BPH和PCa患者以及健康志愿者中验证它们的非侵入性诊断潜力。从组织和血清中分离miRNA,通过逆转录 - 聚合酶链反应(RT - PCR)进行定量,并通过受试者工作特征(ROC)曲线分析评估其作为生物标志物的潜力,随后对每个miRNA进行靶标组分析。
在所评估的非侵入性miRNA中,与对照组相比,在PCa中miRNA 141(P = 0.0003)和miRNA 1290(P < 0.0001)具有致癌性且表达显著更高,而miRNA 100(P = 0.0002)和miRNA 335是肿瘤抑制因子。对于BPH,miRNA 141(P = 0.003)和miRNA 335(P = 0.0002)分别被发现具有显著致癌性和肿瘤抑制作用。miRNA组(miRNA - 141、- 1290和- 100)的ROC曲线分析显示曲线下面积显著,具有更高的敏感性和特异性。此外,对其各自靶标组的计算机模拟预测表明它们广泛参与PCa进展以及有助于PCa网络的各种其他级联反应。
据我们所知,我们将首次报道这组可用于准确、高效地从健康男性中诊断BPH和PCa患者的miRNA。