Perrot-Applanat Martine, Vacher Sophie, Pimpie Cynthia, Chemlali Walid, Derieux Simon, Pocard Marc, Bieche Ivan
INSERM U965, Lariboisiere Hospital, University of Paris-Diderot-Paris 7, 75010 Paris, France.
Department of Genetics, Pharmacogenomics Unit-Institut Curie, University of Paris-Descartes-Paris 5, 75005 Paris, France.
Oncol Lett. 2019 Jul;18(1):674-686. doi: 10.3892/ol.2019.10392. Epub 2019 May 21.
Gastric cancer (GC) is a highly heterogeneous disease and one of the major causes of cancer-related mortality worldwide. Diffuse-type gastric adenocarcinoma (or poorly cohesive- with independent cells) is characterized by aggressive behavior (rapid invasion, chemoresistance and peritoneal metastasis), as compared with intestinal-subtype adenocarcinoma. Diffuse subtype GC additionally has a substantially increasing incidence rate in Europe and the USA, and was often associated with younger age. Our objective was to analyze the expression and clinical significance of genes involved in several signaling pathways in diffuse-type GC. Tumors samples and non-malignant gastric tissues were obtained from patients with GC (diffuse-type and intestinal-subtype adenocarcinoma). The expression of 33 genes coding for proteins involved in four categories, growth factors and receptors, epithelial-mesenchymal transition, cell proliferation and migration, and angiogenesis was determined by reverse transcription-quantitative polymerase chain reaction. The expression of 22 genes was significantly upregulated in diffuse-type GC and two were downregulated (including ) compared with normal tissues. Among these genes, acompared with intestinal-subtype adenocarcinoma, diffuse-type GC revealed elevated levels of and and and , and decreased levels of and . The expression of selected genes was compared with other genes and according to clinical parameters. Furthermore, expression was significantly increased in linitis, a sub-population of diffusely infiltrating type associated with extensive fibrosis and tumor invasion. Our study identified new target genes ( and ) whose expression is associated with aggressive phenotype of diffuse-type GC.
胃癌（GC）是一种高度异质性疾病，也是全球癌症相关死亡的主要原因之一。弥漫型胃腺癌（或低黏附性——细胞独立存在）与肠型腺癌相比，具有侵袭性强（快速侵袭、化疗耐药和腹膜转移）的特点。弥漫型GC在欧洲和美国的发病率还在大幅上升，且常与较年轻的年龄相关。我们的目的是分析弥漫型GC中参与几种信号通路的基因的表达及临床意义。肿瘤样本和非恶性胃组织取自GC患者（弥漫型和肠型腺癌）。通过逆转录-定量聚合酶链反应测定了33个编码参与四类蛋白质（生长因子和受体、上皮-间质转化、细胞增殖和迁移以及血管生成）的基因的表达。与正常组织相比，弥漫型GC中有22个基因的表达显著上调，2个基因下调（包括 ）。在这些基因中，与肠型腺癌相比，弥漫型GC中 、 、 和 的水平升高，而 和 的水平降低。将所选基因的表达与其他基因进行比较，并根据临床参数进行分析。此外，在皮革胃（一种与广泛纤维化和肿瘤侵袭相关的弥漫浸润型亚群）中， 表达显著增加。我们的研究确定了新的靶基因（ 和 ），其表达与弥漫型GC的侵袭性表型相关。
