Magarifuchi Naomi, Iwasaki Takeshi, Katayama Yoshihiro, Tomonaga Takumi, Nakashima Miya, Narutomi Fumiya, Kato Kiyoko, Oda Yoshinao
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.
Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka 812-8582, Japan.
Oncol Lett. 2024 Mar 7;27(5):196. doi: 10.3892/ol.2024.14329. eCollection 2024 May.
Ovarian high-grade serous carcinoma (OHGSC) is the most common type of ovarian cancer worldwide. Genome sequencing has identified mutations in chromatin remodeling factors (CRFs) in gynecological cancer, such as clear cell carcinoma, endometrioid carcinoma and endometrial serous carcinoma. However, to the best of our knowledge, the association between CRFs and OHGSC remains unexplored. The present study aimed to investigate the clinicopathological and molecular characteristics of CRF dysfunction in OHGSC. CRF alterations were analyzed through numerous methods, including the analysis of public next-generation sequencing (NGS) data from 585 ovarian serous carcinoma cases from The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC), and DNA copy number assays, which were performed on 203 surgically resected OHGSC samples. In the public NGS dataset, the most frequent genetic alteration was actin-like protein 6A () amplification at 19.5%. Switch/sucrose non-fermentable related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 () amplification (3.1%) was associated with significantly decreased overall survival (OS). In addition, chromodomain-helicase-DNA-binding protein 4 () amplification (5.7%) exhibited unfavorable outcome trends, although not statistically significant. IHC revealed the protein expression loss of ARID1A (2.5%), SMARCA2 (2.5%) and SMARCA4 (3.9%). The protein expression levels of ACTL6A, SMARCC2 and CHD4 were evaluated using H-score. Patients with low protein expression levels of ACTL6A showed a significantly decreased OS. Copy number gain or gene amplification was demonstrated in (66.2%) and (33.5%), while shallow deletion or deep deletion was demonstrated in (70.7%). However, there was no statistically significant difference in protein levels of these CRFs, between the different copy number alterations (CNAs). Overall, OHGSC exhibited CNAs and protein loss, indicating possible gene alterations in CRFs. Moreover, there was a significant association between the protein expression levels of ACTL6A and poor prognosis. Based on these findings, it is suggested that CRFs could serve as prognostic markers for OHGSC.
卵巢高级别浆液性癌（OHGSC）是全球最常见的卵巢癌类型。基因组测序已在妇科癌症中鉴定出染色质重塑因子（CRFs）的突变，如透明细胞癌、子宫内膜样癌和子宫内膜浆液性癌。然而，据我们所知，CRFs与OHGSC之间的关联仍未得到探索。本研究旨在调查OHGSC中CRF功能障碍的临床病理和分子特征。通过多种方法分析CRF改变，包括对来自癌症基因组图谱（TCGA）的585例卵巢浆液性癌病例的公开二代测序（NGS）数据进行分析、免疫组织化学（IHC）以及对203例手术切除的OHGSC样本进行DNA拷贝数测定。在公开的NGS数据集中，最常见的基因改变是肌动蛋白样蛋白6A（）扩增，占19.5%。与蔗糖非发酵相关的开关/基质相关、肌动蛋白依赖性染色质调节因子亚家族c成员2（）扩增（3.1%）与总生存期（OS）显著降低相关。此外，染色质结构域解旋酶DNA结合蛋白4（）扩增（5.7%）呈现出不良预后趋势，尽管无统计学意义。免疫组化显示ARID1A（2.5%）、SMARCA2（2.5%）和SMARCA4（3.9%）蛋白表达缺失。使用H评分评估ACTL6A、SMARCC2和CHD4的蛋白表达水平。ACTL6A蛋白表达水平低的患者总生存期显著降低。（66.2%）和（33.5%）显示出拷贝数增加或基因扩增，而（70.7%）显示出浅缺失或深缺失。然而，在不同的拷贝数改变（CNAs）之间，这些CRFs的蛋白水平无统计学显著差异。总体而言，OHGSC表现出CNAs和蛋白缺失，表明CRFs可能存在基因改变。此外，ACTL6A蛋白表达水平与不良预后之间存在显著关联。基于这些发现，提示CRFs可作为OHGSC的预后标志物。
