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Ras 相关结构域家族蛋白 1A 甲基化和 PD-L1 表达与卵巢癌的关系:一项 112 例回顾性研究。

Ras association domain family protein 1a hypermethylation and PD-L1 expression in ovarian cancer: A retrospective study of 112 cases.

机构信息

Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2019 Sep;240:103-108. doi: 10.1016/j.ejogrb.2019.06.015. Epub 2019 Jun 13.

Abstract

OBJECTIVE

This study assessed the interrelationships between Ras association domain family protein 1a (RASSF1A) gene hypermethylation, PD-L1 protein expression, and the clinicopathological characteristics of 112 ovarian cancer (OC) samples.

METHODS

Formalin-fixed paraffin-embedded OC tissue samples from surgical resection were assessed. Bisulfite pyrosequencing and immunohistochemistry were applied to detect RASSF1A gene methylation and PD-L1 protein expression in tumor cells, respectively. RASSF1A gene methylation and PD-L1 protein expression levels were analyzed against clinicopathological features and prognosis through standard statistical methods.

RESULTS

Of the 112 OC samples, 49.1% (55/112) exhibited RASSF1A gene hypermethylation. The frequency of RASSF1A hypermethylation was significantly higher in nonserous subtype (73.0%), early stage (66.7%), and nonrecurrent OC (62.9%, p < 0.05). Among all samples, 61.6% (69/112) were positive for PD-L1 protein expression in tumor cells. No significant differences in PD-L1 expression were identified for age, menstrual status, histological type, tumor location, grade, stage, lymph node metastasis, or prognosis (p > 0.05). RASSF1A methylation and PD-L1 expression were not correlated (p > 0.05).

CONCLUSIONS

This was the first study linking RASSF1A hypermethylation variability to PD-L1 expression and clinicopathological characteristics of OC. Epigenetic alteration of RASSF1A was closely associated with nonserous subtype, early stage, and nonrecurrent OC, indicating that RASSF1A hypermethylation may play a role in early detection of OC. Expression of PD-L1 had no relationship with the studied clinicopathological characteristics or RASSF1A hypermethylation in the 112 OC samples.

摘要

目的

本研究评估了 Ras 相关结构域家族蛋白 1a(RASSF1A)基因甲基化、PD-L1 蛋白表达与 112 例卵巢癌(OC)样本临床病理特征之间的相互关系。

方法

评估了来自手术切除的福尔马林固定石蜡包埋 OC 组织样本。分别应用亚硫酸氢盐焦磷酸测序和免疫组织化学检测肿瘤细胞中 RASSF1A 基因甲基化和 PD-L1 蛋白表达。通过标准统计方法分析 RASSF1A 基因甲基化和 PD-L1 蛋白表达水平与临床病理特征和预后的关系。

结果

在 112 例 OC 样本中,49.1%(55/112)存在 RASSF1A 基因甲基化。非浆液性亚型(73.0%)、早期(66.7%)和非复发性 OC(62.9%,p<0.05)中 RASSF1A 过度甲基化的频率明显更高。在所有样本中,肿瘤细胞中 PD-L1 蛋白表达阳性的比例为 61.6%(69/112)。PD-L1 表达在年龄、月经状况、组织学类型、肿瘤位置、分级、分期、淋巴结转移或预后方面无显著差异(p>0.05)。RASSF1A 甲基化和 PD-L1 表达之间无相关性(p>0.05)。

结论

这是首次将 RASSF1A 过度甲基化的变异性与 OC 的 PD-L1 表达和临床病理特征联系起来的研究。RASSF1A 的表观遗传学改变与非浆液性亚型、早期和非复发性 OC 密切相关,表明 RASSF1A 过度甲基化可能在 OC 的早期检测中发挥作用。在 112 例 OC 样本中,PD-L1 的表达与所研究的临床病理特征或 RASSF1A 过度甲基化无关。

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