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Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients
Disease Markers Pub Date : 2021-07-29 , DOI: 10.1155/2021/9980410
Jean Paul Nshizirungu 1 , Sanae Bennis 1 , Ihsane Mellouki 2 , Mohammed Sekal 3 , Dafr-Allah Benajah 4 , Nada Lahmidani 4 , Hicham El Bouhaddouti 5 , Karim Ibn Majdoub 5 , Sidi Adil Ibrahimi 4 , Sónia Pires Celeiro 6, 7 , Marta Viana-Pereira 6, 7 , Fernanda Franco Munari 8 , Guilherme Gomes Ribeiro 9 , Vinicius Duval 9 , Iara Santana 9 , Rui Manuel Reis 6, 7, 8
Affiliation  

Introduction. The Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis. Methods. Ninety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI). Results. Our results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.

中文翻译:

癌症基因组图谱 (TCGA) 和亚洲癌症研究小组 (ACRG) 胃癌分子分类的复制及其与摩洛哥患者临床病理学特征和总体生存率的关系

简介。癌症基因组图谱 (TCGA) 项目和亚洲癌症研究小组 (ACRG) 最近将胃癌分为分子亚型。然而,这些分类系统需要高成本和复杂的分子技术,阻碍了它们在临床中的广泛使用。本研究旨在利用一系列摩洛哥胃癌患者的常规诊断实践中可用的技术生成胃癌的分子亚型。此外,我们评估了分子亚型、临床病理学特征和预后之间的关联。方法. 97 例胃癌病例根据 TCGA、ACRG 和使用一组四种分子标志物(EBV、MSI、E-cadherin 和 p53)的综合分类进行分类。还评估了 HER2 状态和 PD-L1 表达。使用免疫组织化学(E-cadherin、p53、HER2 和 PD-L1)、原位杂交(EBV 和 HER2 模棱两可的情况)和多重 PCR (MSI) 分析这些标志物。结果. 我们的结果表明,这些亚型呈现出不同的临床病理学特征和预后。EBV 阳性胃癌仅在男性患者中发现。GS(TCGA 分类)、MSS/EMT(ACRG 分类)和 E-cadherin 异常亚型(综合分类)呈现 Lauren 弥漫性组织学富集,并倾向于在年轻时被诊断出来。在所有分类(TCGA、ACRG 和综合分类)中,MSI 亚型与更好的总生存期相关。在 EBV 亚型(TCGA 和综合分类)和 MSS/EMT 亚型(ACRG 分类)中观察到最差的预后。讨论/结论. 我们报告了一种可重复且负担得起的胃癌分型算法,该算法可以使用常规诊断中可用的技术重现最近公认的 TCGA、ACRG 和综合胃癌分类。这些简化的分类不仅可用于分子分类,还可用于预测胃癌患者的预后。
更新日期:2021-07-29
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