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晚期高级别浆液性卵巢癌患者血浆游离DNA甲基化的预后意义

Prognostic Significance of Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer.

作者信息

Tserpeli Victoria, Stergiopoulou Dimitra, Londra Dora, Giannopoulou Lydia, Buderath Paul, Balgkouranidou Ioanna, Xenidis Nikolaos, Grech Christina, Obermayr Eva, Zeillinger Robert, Pavlakis Kitty, Rampias Theodoros, Kakolyris Stylianos, Kasimir-Bauer Sabine, Lianidou Evi S

机构信息

Analysis of Circulating Tumor Cells, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece.

Department of Gynecology and Obstetrics, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.

出版信息

Cancers (Basel). 2021 Dec 21;14(1):4. doi: 10.3390/cancers14010004.

Abstract

BACKGROUND

Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment.

METHODS

In the present study, we examined the methylation status of six gene promoters (, , , , and in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC.

RESULTS

We report for the first time that the DNA methylation of in plasma cfDNA was significantly correlated with worse PFS ( = 0.045) in advanced stage HGSOC.

CONCLUSIONS

Our results strongly indicate that epigenetic inactivation could be a predictor of resistance to platinum drugs in ovarian cancer. Our results should be further validated in studies based on a larger cohort of patients, in order to further explore whether the DNA methylation of promoter could serve as a potential prognostic DNA methylation biomarker and a predictor of resistance to platinum-based chemotherapy in ovarian cancer.

摘要

背景

循环肿瘤DNA(ctDNA)中的表观遗传改变作为新型潜在液体活检生物标志物的来源极具前景,并且在卵巢癌的早期诊断、预后评估及治疗反应监测方面构成了一种非常有前景的液体活检方法。

方法

在本研究中,我们检测了高级别浆液性卵巢癌(HGSOC)中六个基因启动子(,,,,和)的甲基化状态。我们评估了这六个基因启动子的DNA甲基化在早期、晚期和转移性HGSOC患者的原发性肿瘤(福尔马林固定石蜡包埋组织,FFPEs)和血浆游离DNA(cfDNA)样本中的预后意义。

结果

我们首次报道,在晚期HGSOC中,血浆cfDNA中的DNA甲基化与较差的无进展生存期(PFS)显著相关(=0.045)。

结论

我们的结果强烈表明,表观遗传失活可能是卵巢癌对铂类药物耐药的一个预测指标。我们的结果应在基于更大患者队列的研究中进一步验证,以便进一步探索启动子的DNA甲基化是否可作为卵巢癌潜在的预后DNA甲基化生物标志物和铂类化疗耐药的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2943/8750111/4363626ae694/cancers-14-00004-g001.jpg

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