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miR-205 和 miR-34a 在卵巢癌管理中的诊断和治疗潜力:基于 miRNA 靶标的分析。

Diagnostics and Therapeutic Potential of miR-205 and miR-34a in Ovarian Cancer Management: A miRNA-Target-Based Analysis.

机构信息

Department of Biotechnology, Motilal Nehru National Institute of Technology, Allahabad, Prayagraj, India.

Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam, India.

出版信息

DNA Cell Biol. 2023 Mar;42(3):151-162. doi: 10.1089/dna.2022.0487. Epub 2023 Feb 13.

DOI:10.1089/dna.2022.0487
PMID:36779980
Abstract

Epithelial ovarian cancer (EOC) treatment strategies mainly focused on surgery combined with chemotherapy. Recent targeted therapy techniques emerge as milestone and could be used for management of ovarian cancer (OC) progression with more efficacy. The aim is to evaluate the therapeutic and diagnostic potential of microRNA (miRNA) in management of EOC using and quantitative real-time PCR (qRT-PCR) expression analysis. We performed functional enrichment and miRNA-Target genes expression analysis in 48 EOC and 22 normal tissue samples using qRT-PCR and correlated with miRNA expression data in matched samples to evaluate the diagnostic and therapeutic potential of miRNA in OC management. functional enrichment analysis revealed miRNA association with disease. Target genes of miRNAs participate in several biologically important pathways leading to cancer progression. Targets of miRNA-205 and miRNA-34a were significantly downregulated, and upregulated, respectively, in EOC. Moreover, significant negative correlation between relative expression of miRNA-205 and target genes (BCL2, ZEB1, E2F1, and TP53) was observed with  = -0.813;  = -0.755;  = -0.559; and  = -0.767, respectively. Similarly, miRNA-34a also showed higher negative correlation with target genes (MDM4, MAPK3, BRCA1, AREG) with  = -0.840;  = -0.870;  = -0.622; and  = -0.623, respectively. In addition, receiver operating characteristics analysis of combined miRNA panel, miRNA-205-Target gene panel, and miRNA-34a-Target gene panel exhibited higher diagnostics value with area under the curve (AUC) of 92.7 ( < 0.0001), 94.8 ( < 0.0001), and 98.3 ( < 0.0001), respectively. Negative Correlation between miRNA and target genes expression data in matched samples highlights therapeutic potential of miRNA in EOC management. Moreover, combined diagnostic potential of miRNA-target gene panel could predict risk of EOC with higher AUC, sensitivity, and specificity.

摘要

上皮性卵巢癌 (EOC) 的治疗策略主要集中在手术联合化疗上。最近出现的靶向治疗技术是一个里程碑,可更有效地用于卵巢癌 (OC) 进展的治疗管理。目的是通过 和定量实时 PCR (qRT-PCR) 表达分析来评估 miRNA 在 EOC 管理中的治疗和诊断潜力。我们使用 qRT-PCR 在 48 个 EOC 和 22 个正常组织样本中进行了功能富集和 miRNA-靶基因表达分析,并与匹配样本中的 miRNA 表达数据相关联,以评估 miRNA 在 OC 管理中的治疗和诊断潜力。功能富集分析显示 miRNA 与疾病有关。miRNA 的靶基因参与导致癌症进展的几个重要生物途径。miRNA-205 和 miRNA-34a 的靶基因在 EOC 中分别显著下调和上调。此外,miRNA-205 和靶基因 (BCL2、ZEB1、E2F1 和 TP53) 的相对表达之间观察到显著的负相关,  = -0.813;  = -0.755;  = -0.559;  = -0.767,分别。同样,miRNA-34a 与靶基因 (MDM4、MAPK3、BRCA1、AREG) 也表现出更高的负相关性,  = -0.840;  = -0.870;  = -0.622;  = -0.623,分别。此外,联合 miRNA 面板、miRNA-205-靶基因面板和 miRNA-34a-靶基因面板的受试者工作特征分析显示出更高的诊断价值,曲线下面积 (AUC) 分别为 92.7 ( < 0.0001)、94.8 ( < 0.0001) 和 98.3 ( < 0.0001)。匹配样本中 miRNA 和靶基因表达数据之间的负相关突出了 miRNA 在 EOC 管理中的治疗潜力。此外,miRNA-靶基因面板的联合诊断潜力可以通过更高的 AUC、敏感性和特异性来预测 EOC 的风险。

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