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子宫内膜样腺癌不同分子亚型的鉴定

Identification of Distinct Molecular Subtypes of Endometrioid Adenocarcinoma.

作者信息

Lei Jia, Yan Shuping, Guo Xiangqian, Wang Fengling, Zhang Guosen, Kan Quancheng, Guo Ruixia

机构信息

Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Joint National Laboratory for Antibody Drug Engineering, Cell Signal Transduction Laboratory, Department of Preventive Medicine, School of Basic Medical Sciences, Institute of Biomedical Informatics, Henan University, Kaifeng, China.

出版信息

Front Genet. 2021 Jul 21;12:568779. doi: 10.3389/fgene.2021.568779. eCollection 2021.

Abstract

Endometrial carcinoma (EC) is one of the most common gynecological cancers worldwide. Endometrioid adenocarcinoma (EAC) is the major form of EC, accounting for 75-80% of cases. Currently, there is no molecular classification system for EAC, so there are no corresponding targeted treatments. In this study, we identified two distinct molecular subtypes of EAC with different gene expression patterns and clinicopathologic characteristics. Subtype I EAC cases, accounting for the majority of cases (56%), were associated with an earlier stage, a more well-differentiated grade, a lower tumor invasion rate, and a more favorable prognosis, and the median tumor necrosis percent (15%) was also significantly higher in subtype I EAC. In contrast, subtype II EAC represents high-grade EAC, with a higher tumor invasion rate and tumor weight. The up-regulated genes in subtype I EAC were associated with the immune response, defense response, cell motion, and cell motility pathway, whereas the up-regulated genes in subtype II EAC were associated with the cell cycle, DNA replication, and RNA processing pathways. Additionally, we identified three potential subtype-specific biomarkers, comprising (MDM2 proto-oncogene) for subtype I, and (mutS homolog 2) and (mutS homolog 6) for subtype II.

摘要

子宫内膜癌(EC)是全球最常见的妇科癌症之一。子宫内膜样腺癌(EAC)是EC的主要形式,占病例的75 - 80%。目前,EAC尚无分子分类系统,因此也没有相应的靶向治疗方法。在本研究中,我们鉴定出两种具有不同基因表达模式和临床病理特征的EAC分子亚型。I型EAC病例占大多数(56%),与早期阶段、高分化程度、较低的肿瘤侵袭率和更良好的预后相关,并且I型EAC的肿瘤坏死中位数百分比(15%)也显著更高。相比之下,II型EAC代表高级别EAC,具有更高的肿瘤侵袭率和肿瘤重量。I型EAC中上调的基因与免疫反应、防御反应、细胞运动和细胞运动途径相关,而II型EAC中上调的基因与细胞周期、DNA复制和RNA加工途径相关。此外,我们鉴定出三种潜在的亚型特异性生物标志物,包括I型的(MDM2原癌基因),以及II型的(mutS同源物2)和(mutS同源物6)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/316b/8334731/a068edb14e3f/fgene-12-568779-g001.jpg

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