Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy.
Department of Urology, Polyclinic Hospital, University of Catania, 95123 Catania, Italy.
Int J Mol Sci. 2024 Sep 19;25(18):10079. doi: 10.3390/ijms251810079.
RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease's initiation, progression, and treatment response. This study aimed to evaluate the ability of a specific set of RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and mRNAs, to discriminate between PCa and the non-neoplastic condition benign prostatic hyperplasia (BPH). After selecting by literature mining the most relevant RNAs differentially expressed in biofluids from PCa patients, we evaluated their discriminatory power in samples of unfiltered urine from 50 PCa and 50 BPH patients using both real-time PCR and droplet digital PCR (ddPCR). Additionally, we also optimized a protocol for urine sample manipulation and RNA extraction. This two-way validation study allowed us to establish that miRNAs (i.e., miR-27b-3p, miR-574-3p, miR-30a-5p, and miR-125b-5p) are more efficient biomarkers for PCa compared to long RNAs (mRNAs and lncRNAs) (e.g., PCA3, PCAT18, and KLK3), as their dysregulation was consistently reported in the whole urine of patients with PCa compared to those with BPH in a statistically significant manner regardless of the quantification methodology performed. Moreover, a significant increase in diagnostic performance was observed when molecular signatures composed of different miRNAs were considered. Hence, the abovementioned circulating ncRNAs represent excellent potential non-invasive biomarkers in urine capable of effectively distinguishing individuals with PCa from those with BPH, potentially reducing cancer overdiagnosis.
RNAs，尤其是非编码 RNA（ncRNAs），由于其与其他分子相互作用并调节其他分子的能力，在调节细胞机制中起着至关重要的作用。ncRNAs 的表达模式在前列腺癌（PCa）中发生改变，导致疾病的发生、发展和治疗反应。本研究旨在评估一组特定的 RNA，包括长 ncRNAs（lncRNAs）、microRNAs（miRNAs）和 mRNAs，在区分 PCa 和非肿瘤性良性前列腺增生（BPH）方面的能力。通过文献挖掘选择了在 PCa 患者生物流体中差异表达的最相关 RNA 后，我们使用实时 PCR 和液滴数字 PCR（ddPCR）评估了它们在 50 例 PCa 和 50 例 BPH 患者的未过滤尿液样本中的区分能力。此外，我们还优化了尿液样本处理和 RNA 提取的方案。这项双向验证研究使我们能够确定，miRNAs（即 miR-27b-3p、miR-574-3p、miR-30a-5p 和 miR-125b-5p）比长 RNA（mRNA 和 lncRNA）（例如 PCA3、PCAT18 和 KLK3）更适合作为 PCa 的生物标志物，因为它们在患有 PCa 的患者的整个尿液中失调的情况比患有 BPH 的患者更为一致，且无论使用何种定量方法，差异均具有统计学意义。此外，当考虑由不同 miRNAs 组成的分子特征时，诊断性能显著提高。因此，上述循环 ncRNAs 代表了尿液中具有良好潜力的非侵入性生物标志物，能够有效区分 PCa 患者和 BPH 患者，可能减少癌症过度诊断。
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