Shutko E V, Bryzgunova O E, Ostaltsev I A, Laktionov P P, Konoshenko M Y
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Academician Lavrentyev Avenue 8, Novosibirsk, 630090, Russia.
Novosibirsk State University, 630090, Novosibirsk, Russia.
Med Oncol. 2025 Apr 28;42(6):185. doi: 10.1007/s12032-025-02730-4.
Prostate cancer (PC) is one of the most common oncological diseases. Maximal androgen blockade (MAB) is used at different stages of treatment, including prior to radical prostatectomy (RP). The data on the expression of extracellular miRNAs involved in carcinogenesis before and after MAB/RP's are demanded for the selection of miRNAs markers for the diagnostics of PC and the effectiveness of PC treatment as well as insight of these miRNAs and their regulated genes involvement in oncogenesis. The aim of this study was to screen 13 miRNAs associated with PC from urine extracellular vesicles (EVs) of healthy donors (HD) and PC patients before and after MAB, RP, and MAB followed RP in looking for correlations with PC and PC treatment/clinical characteristics followed by identification of the most distinctive miRNA signatures as set of markers for the future extensive verification. Urine samples were collected from HD and PC patients, both those who had undergone neoadjuvant therapy and those who had not, prior to radical prostatectomy (RP) and one-week post-surgery. EVs were isolated using the aggregation-precipitation method, and miRNAs within EVs were extracted using glass fiber sorbents. The quantification of the 13 miRNAs was performed using reverse transcription TaqMan PCR (RT-PCR), with subsequent paired ratio-based normalization followed by the selection of miRNA ratios differentially expressed between the comparison groups from the set of all miRNA pairs. A comparative analysis of the relative expression of miRNAs in the urine of PC patients versus HD was conducted, revealing 49 ratios of differentially expressed miRNAs influenced by therapy. The study identified specific miRNAs with significant expression changes due to various treatments: influence of MAB, RP, and RP in patients after neoadjuvant MAB, as well as under the influence of MAB followed by RP. The relative expression of the extracellular miRNAs studied was influenced by the type and combination of various PC treatments, which indicates the prospects of specific miRNA predictors of PC treatment effectiveness.
前列腺癌（PC）是最常见的肿瘤疾病之一。最大雄激素阻断（MAB）用于治疗的不同阶段，包括在根治性前列腺切除术（RP）之前。在MAB/RP前后，参与致癌过程的细胞外微小RNA（miRNA）的表达数据对于选择用于PC诊断、PC治疗效果评估的miRNA标志物，以及深入了解这些miRNA及其调控基因在肿瘤发生中的作用至关重要。本研究的目的是从健康供体（HD）以及PC患者在MAB、RP以及MAB后接RP之前和之后的尿液细胞外囊泡（EVs）中筛选与PC相关的13种miRNA，寻找其与PC及PC治疗/临床特征的相关性，随后鉴定出最具特色的miRNA特征作为未来广泛验证的标志物集。在根治性前列腺切除术（RP）前及术后一周，从HD和PC患者（包括接受过新辅助治疗和未接受过新辅助治疗的患者）中收集尿液样本。使用聚集沉淀法分离EVs，并使用玻璃纤维吸附剂提取EVs中的miRNA。使用逆转录TaqMan PCR（RT-PCR）对13种miRNA进行定量，随后进行基于配对比值的标准化，然后从所有miRNA对中选择比较组之间差异表达的miRNA比值。对PC患者与HD尿液中miRNA的相对表达进行了比较分析，发现49种受治疗影响的差异表达miRNA比值。该研究确定了由于各种治疗导致表达有显著变化的特定miRNA：MAB、RP以及新辅助MAB后患者接受RP的影响，以及MAB后接RP的影响。所研究的细胞外miRNA的相对表达受各种PC治疗的类型和组合影响，这表明特定miRNA作为PC治疗效果预测指标的前景。
