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患者血浆的转录组分析显示,循环miR200c是高级别浆液性卵巢癌的潜在生物标志物。

Transcriptomic analysis of patient plasma reveals circulating miR200c as a potential biomarker for high-grade serous ovarian cancer.

作者信息

Hannan Natalie J, Cohen Paul A, Beard Sally, Bilic Sanela, Zhang Bonnie, Tong Stephen, Whitehead Clare, Hui Lisa

机构信息

Therapeutics Discovery and Vascular Function Group, University of Melbourne, Heidelberg, Victoria, Australia.

Translational Obstetrics Group, University of Melbourne, Heidelberg, Victoria, Australia.

出版信息

Gynecol Oncol Rep. 2021 Dec 2;39:100894. doi: 10.1016/j.gore.2021.100894. eCollection 2022 Feb.

Abstract

BACKGROUND

High-grade serous tubo-ovarian cancer (HGSC) is the most common histological subtype of epithelial ovarian cancer, and highly lethal. Currently there is no effective screening test and prognosis is poor as the majority of cases are diagnosed at the advanced stage. Cell free RNAs including microRNAs (miRNAs) are dysregulated in ovarian cancer tissue and are detectable in the circulation. This study aimed to determine whether circulating cell free miRNAs may be potential biomarkers for the detection of HGSC.

METHODS

Plasma was collected from women with HGSC (Grade 3, n = 24), and benign ovarian masses (n = 24). RNA was extracted from patient plasma and subjected to miRNA targeted next generation sequencing (NGS). A subsequent validation cohort was assessed using plasma collected from women with HGSC (n = 14) and controls (with a benign ovarian mass; n = 15). RNA was extracted and assessed using quantitative RT-PCR.

RESULTS

Differential gene expression (DGE) of the NGS data revealed a significant increase in the miRNA, miR200c, in the circulation of women with HGSC (p less than 0.05) compared to controls. In the validation cohort miR200c expression by qPCR was found to also be increased in the circulation of women with HGSC compared to controls (p = 0.0023).

CONCLUSIONS

Circulating miR200c may be a promising candidate biomarker for the detection of HGSC. Further larger cohort studies exploring earlier stages are needed to determine whether circulating miR200c may be a sensitive and specific biomarker of tubo-ovarian cancer.

摘要

背景

高级别浆液性输卵管卵巢癌(HGSC)是上皮性卵巢癌最常见的组织学亚型,且具有高度致死性。目前尚无有效的筛查检测方法,由于大多数病例在晚期才被诊断出来,其预后较差。包括微小RNA(miRNA)在内的游离RNA在卵巢癌组织中表达失调,且可在循环中检测到。本研究旨在确定循环游离miRNA是否可能是检测HGSC的潜在生物标志物。

方法

收集HGSC患者(3级,n = 24)和良性卵巢肿块患者(n = 24)的血浆。从患者血浆中提取RNA,并进行miRNA靶向新一代测序(NGS)。随后使用从HGSC患者(n = 14)和对照组(患有良性卵巢肿块;n = 15)收集的血浆对验证队列进行评估。提取RNA并使用定量逆转录聚合酶链反应(qRT-PCR)进行评估。

结果

NGS数据的差异基因表达(DGE)显示,与对照组相比,HGSC患者循环中的miRNA miR200c显著增加(p < 0.05)。在验证队列中,通过qPCR发现HGSC患者循环中的miR200c表达也高于对照组(p = 0.0023)。

结论

循环miR200c可能是检测HGSC的一个有前景的候选生物标志物。需要进一步开展更大规模的队列研究以探索更早阶段情况,来确定循环miR200c是否可能是输卵管卵巢癌的敏感和特异生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac95/8717717/746027d5ba75/gr1.jpg

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