Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Faculty of Medicine and Pharmacy, Abdelmalek Essaadi University, Tangier, Morocco.
Genet Test Mol Biomarkers. 2021 Feb;25(2):116-123. doi: 10.1089/gtmb.2020.0146.
To investigate correlations between microsatellite instability (MSI) and the phenotype, clinicopathological features, and overall survival (OS) in Moroccan gastric cancer (GC) patients. We evaluated the mutation frequency of 22 MSI-target genes in MSI-positive tumors. MSI evaluation were performed for 97 gastric tumors by multiplex polymerase chain reaction (PCR) using a panel of five quasimonomorphic mononucleotide repeat markers (NR27, NR21, NR24, BAT25, and BAT26). The mutation profiles of 22 MSI-target genes were assessed by multiplex PCR and genotyping. Kaplan-Meier curves, the log-rank test, and the Cox proportional hazard regression model were used to conduct survival analyses. Microsatellite stable (MSS) status was observed in 77/97 (79.4%) gastric cancer samples, MSI-Low in 7 (7.2%) samples, and MSI-High (MSI-H) in 13 (13.4%) cases. The MSI-H phenotype was significantly associated with older age ( = 0.004), tumor location ( < 0.001), and intestinal-type of Lauren classification ( < 0.001). Among the 22 MSI target genes analyzed, the most frequently altered genes were (84.6%), (30.8%), (23.1%), (23.1%), and (23.1%). Multivariate analysis revealed the MSS phenotype (Hazard ratio, 0.23; 95% confidence interval, 0.7-7.4; = 0.014) as an independent indicator of poor prognosis in our population. This study is the first analysis of MSI in Moroccan GC patients. MSI-H GCs have distinct clinicopathological features and an improved OS. We have identified candidate target genes altered in MSI-positive tumors with potential clinical implications. These findings can guide immunotherapy designed for Moroccan GC patients.
为了研究微卫星不稳定性（MSI）与摩洛哥胃癌（GC）患者表型、临床病理特征和总生存期（OS）之间的相关性。我们评估了 22 个 MSI 靶基因在 MSI 阳性肿瘤中的突变频率。通过使用 5 个拟单核苷酸重复标记物（NR27、NR21、NR24、BAT25 和 BAT26）的多重聚合酶链反应（PCR）对 97 例胃肿瘤进行 MSI 评估。通过多重 PCR 和基因分型评估了 22 个 MSI 靶基因的突变谱。采用 Kaplan-Meier 曲线、对数秩检验和 Cox 比例风险回归模型进行生存分析。77/97（79.4%）例胃癌样本为微卫星稳定（MSS）状态，7 例（7.2%）为 MSI-Low，13 例（13.4%）为 MSI-High（MSI-H）。MSI-H 表型与年龄较大（=0.004）、肿瘤位置（<0.001）和Lauren 分类的肠型（<0.001）显著相关。在分析的 22 个 MSI 靶基因中，最常改变的基因是（84.6%）、（30.8%）、（23.1%）、（23.1%）和（23.1%）。多变量分析显示 MSS 表型（危险比，0.23；95%置信区间，0.7-7.4；=0.014）是我们人群中预后不良的独立指标。本研究是对摩洛哥 GC 患者 MSI 的首次分析。MSI-H GC 具有独特的临床病理特征和改善的 OS。我们已经确定了 MSI 阳性肿瘤中改变的候选靶基因，具有潜在的临床意义。这些发现可以指导针对摩洛哥 GC 患者的免疫治疗。
