De Re Valli, Alessandrini Lara, Brisotto Giulia, Caggiari Laura, De Zorzi Mariangela, Casarotto Mariateresa, Miolo Gianmaria, Puglisi Fabio, Garattini Silvio Ken, Lonardi Sara, Cannizzaro Renato, Canzonieri Vincenzo, Fassan Matteo, Steffan Agostino
Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padova, 35128 Padova, Italy.
Cancers (Basel). 2022 Feb 28;14(5):1266. doi: 10.3390/cancers14051266.
Trastuzumab is a human epidermal growth factor receptor 2 (HER2) inhibitor used to treat HER2+ metastatic gastric cancer (mGC). The present study aims to investigate the relationship between mRNA expression and HER2-positivity in mGC using a multiplexed gene expression profile in two series of gastric cancer (GC): Series 1 ( = 38): HER2+ and HER2- mGC; Series 2 ( = 36) HER2- GC with and without metastasis. To confirm the results, the same expression profiles were analyzed in 354 GC from The Cancer Genome Atlas (TCGA) dataset. The difference in gene expression connected overexpression with canonical wingless-type (Wnt)/β-catenin pathway and immunohistochemical (IHC) expression loss of E-cadherin (E-CAD). mRNA expression was simultaneously associated with the rs16260-A variant and an increase in E-CAD expression. Differences in retinoic acid receptor alfa (), (coding for the 60S ribosomal L19 protein), catenin delta 1 (), and epidermal growth factor () mRNA levels-all included in the Wnt/β-catenin pathway-were found associated with overall survival (OS). , , and resulted in independent OS prognostic factors. was confirmed as an independent factor along with TNM stage in HER2-overpressed mGC from TCGA collection. Our study highlighted factors involved in the WNT/β-catenin pathway that interconnected E-CAD with overexpression and patient survival.
曲妥珠单抗是一种用于治疗HER2阳性转移性胃癌（mGC）的人表皮生长因子受体2（HER2）抑制剂。本研究旨在通过对两个胃癌（GC）系列进行多重基因表达谱分析，研究mGC中mRNA表达与HER2阳性之间的关系：系列1（n = 38）：HER2阳性和HER2阴性mGC；系列2（n = 36）：有或无转移的HER2阴性GC。为了证实结果，在来自癌症基因组图谱（TCGA）数据集的354例GC中分析了相同的表达谱。基因表达差异将过表达与经典无翅型（Wnt）/β-连环蛋白途径以及E-钙黏蛋白（E-CAD）的免疫组织化学（IHC）表达缺失联系起来。mRNA表达同时与rs16260-A变体和E-CAD表达增加相关。视黄酸受体α（RARA）、RPL19（编码60S核糖体L19蛋白）、连环蛋白δ1（CTNND1）和表皮生长因子（EGF）mRNA水平的差异——均包含在Wnt/β-连环蛋白途径中——被发现与总生存期（OS）相关。RARA、CTNND1和EGF导致独立的OS预后因素。在来自TCGA数据集的HER2过表达mGC中，RARA与TNM分期一起被确认为独立因素。我们的研究强调了WNT/β-连环蛋白途径中涉及的因素，这些因素将E-CAD与HER2过表达和患者生存联系起来。
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