miR-145-5p: A Potential Biomarker in Predicting Gleason Upgrading of Prostate Biopsy Samples Scored 3+3=6.
miR-145-5p: A Potential Biomarker in Predicting Gleason Upgrading of Prostate Biopsy Samples Scored 3+3=6.
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miR-145-5p：预测前列腺活检样本格里森升级的潜在生物标志物得分 3 3=6
DOI：
10.2147/cmar.s336671
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发表时间：
2021
影响因子：
3.3
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wang T;Dong L;Sun J;Shao J;Zhang J;Chen S;Wang C;Wu G;Wang X
Gleason分级系统是用于预测前列腺癌（PCa）行为的主要工具。由于异质性和抽样误差，即使在具有相同Gleason评分（GS）的患者中，预后也是可变的。因此，需要补充Gleason系统的更准确的生物标志物来改善PCa的临床管理。福尔马林固定、石蜡包埋的组织样本来自根治性直肠癌切除术（RP）（患者组1，n=53）和穿刺活检（患者组2，n=107;患者组3，n=119）。使用激光捕获显微切割分别收集来自每个Gleason模式（GP）的纯区域的癌组织，随后进行实时PCR以确定miRNA（包括miR-1- 5 p、miR-21- 5 p、miR-30 d-5 p、miR-100- 5 p、miR-145- 5 p、miR-224- 5 p和miR-708- 5 p）的相对表达。采用受试者操作特征曲线（ROC）和多变量logistic回归分析评估miRNA与Gleason升级（GU）的相关性。通过对miRNA靶点的整合预测和富集分析，确定miRNA的潜在功能。发现与GS 7患者相比，来自根治性前列腺切除术（RP）的GP 3中的miR-145- 5 p在GS 6 PCa患者中过表达，这在更大的活检队列中得到进一步证实。ROC曲线分析显示，活检组织中的miR-145- 5 p与RP后GU显著相关。在多变量分析中，miR-145- 5 p是GU的独立预测因子。我们的研究表明，从纯GS 6和GS 7 PCa的GP 3中存在差异表达的miRNA，突出了一个路径，走向临床使用的miRNA预测GU和辅助治疗方式的选择。
The Gleason grading system is a major tool used for prediction of prostate cancer (PCa) behavior. Because of heterogeneity and sampling errors, prognosis is variable even among patients with the same Gleason score (GS). Therefore, more accurate biomarkers that complement the Gleason system are needed to improve the clinical management of PCa. Formalin-fixed, paraffin embedded tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n=53) and needle biopsy (patient set 2, n=107; patient set 3, n=119). Cancer tissues from pure regions of each Gleason pattern (GP) were separately collected using laser-captured microdissection, followed by Real-time-PCR to determine the relative expression of miRNAs, including miR-1-5p, miR-21-5p, miR-30d-5p, miR-100-5p, miR-145-5p, miR-224-5p, and miR-708-5p. miRNA’s association with Gleason upgrading (GU) was evaluated using receiver operator characteristics (ROC) curve and multivariate logistic regression analysis. The integrated miRNA targets prediction and enrichment analyses were performed to determine the potential functions of miRNA. It was found that miR-145-5p in GP3 from radical prostatectomy (RP) were overexpressed in patients with GS6 PCa compared with GS7 patients, which was further confirmed in a larger biopsy cohort. ROC curve analysis revealed that miR-145-5p in biopsy was significantly associated with GU upon RP. In multivariate analyses, miR-145-5p was an independent predictor of GU. Our study indicated that differential expression of miRNAs existed in GP3 from pure GS6 and GS7 PCa, highlighting a path toward the clinical use of miRNAs in predicting GU and assisting in treatment modality selection.