Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Department of Gastroenterology, Faculty of Medicine and Pharmacy, Abdelmalek Essaadi University, Tangier, Morocco.
Dis Markers. 2021 Jul 28;2021:9980410. doi: 10.1155/2021/9980410. eCollection 2021.
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.
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).
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). . 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.
癌症基因组图谱（TCGA）项目和亚洲癌症研究组织（ACRG）最近将胃癌分为分子亚型。然而，这些分类系统需要高昂的成本和复杂的分子技术，因此无法在临床广泛应用。本研究旨在使用摩洛哥一系列胃癌患者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、临床病理特征和预后之间的关联。
根据 TCGA、ACRG 和使用四个分子标志物（EBV、MSI、E-钙黏蛋白和 p53）的综合分类，对 97 例胃癌病例进行分类。还评估了 HER2 状态和 PD-L1 表达。使用免疫组织化学（E-钙黏蛋白、p53、HER2 和 PD-L1）、原位杂交（EBV 和 HER2 不确定病例）和多重 PCR（MSI）分析这些标志物。
我们的结果表明，这些亚型具有不同的临床病理特征和预后。仅在男性患者中发现 EBV 阳性胃癌。GS（TCGA 分类）、MSS/EMT（ACRG 分类）和 E-钙黏蛋白异常亚型（综合分类）呈现弥漫性组织学丰富的Lauren 组织学，并倾向于在更年轻的年龄诊断。MSI 亚型在所有分类（TCGA、ACRG 和综合分类）中均与总体生存时间延长相关。EBV 亚型（TCGA 和综合分类）和 MSS/EMT 亚型（ACRG 分类）的预后最差。我们报告了一种可重现且经济实惠的胃癌亚分型算法，该算法可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。
