Cordova-Delgado Miguel, Pinto Mauricio P, Retamal Ignacio N, Muñoz-Medel Matías, Bravo María Loreto, Fernández María F, Cisternas Betzabé, Mondaca Sebastián, Sanchez César, Galindo Hector, Nervi Bruno, Ibáñez Carolina, Acevedo Francisco, Madrid Jorge, Peña José, Koch Erica, Maturana Maria José, Romero Diego, de la Jara Nathaly, Torres Javiera, Espinoza Manuel, Balmaceda Carlos, Liao Yuwei, Li Zhiguang, Freire Matías, Gárate-Calderón Valentina, Cáceres Javier, Sepúlveda-Hermosilla Gonzalo, Lizana Rodrigo, Ramos Liliana, Artigas Rocío, Norero Enrique, Crovari Fernando, Armisén Ricardo, Corvalán Alejandro H, Owen Gareth I, Garrido Marcelo
Hematology & Oncology Department, Faculty of Medicine, Pontificia Universidad Católica de Chile (PUC), Santiago 8330032, Chile.
Faculty of Chemical & Pharmaceutical Sciences, Universidad de Chile, Santiago 8380494, Chile.
Cancers (Basel). 2019 Aug 30;11(9):1275. doi: 10.3390/cancers11091275.
Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; = 90) and next generation sequencing (NGS; = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, and were the most frequently altered genes. However, NGS demonstrated the presence of , , and variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.
胃癌（GC）是一种异质性疾病。这种异质性不仅适用于形态和表型特征，也适用于发病率和死亡率的地理差异。由于智利是南美洲死亡率最高的国家之一，我们试图确定智利胃癌的分子特征（ClinicalTrials.gov标识符：NCT03158571/（FORCE1））。从224例患者中获取实体瘤样本和临床数据，通过组织微阵列（TMA；n = 90）和下一代测序（NGS；n = 101）对亚组进行分析。大多数人口统计学和临床数据与先前报告一致。TMA数据表明，60%的患者显示出潜在可操作的改变。此外，20.5%被归类为具有高肿瘤突变负担，13%具有微卫星不稳定性（MSI）。结果还证实了先前的研究报告，即智利来源的GC样本中爱泼斯坦-巴尔病毒（EBV）阳性率较高（13%），这表明高比例的患者可能从免疫治疗中获益。正如预期的那样，KRAS和NRAS是最常发生改变的基因。然而，NGS显示存在当前GC数据库中先前未报告的BRAF、PIK3CA和ARID1A变体。最后，使用肯德尔方法，我们报告EBV+状态与程序性死亡配体-1（PDL1）+之间存在显著相关性，p53突变状态与MSI之间存在负相关性。我们的结果表明，在这个智利队列中，高比例的患者是免疫治疗的潜在候选者。据我们所知，这项研究是南美洲第一项评估可操作靶点患病率并检查GC患者分子特征的研究。
