Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mol Cancer Res. 2018 Sep;16(9):1420-1429. doi: 10.1158/1541-7786.MCR-17-0467. Epub 2018 May 21.
Hematogenous recurrence is a challenging clinical finding that often leads to fatalities of patients with gastric cancer. Therefore, the identification of specific biomarkers and potential therapeutic target molecules for hematogenous recurrence is required to improve the outcomes of these patients. Here, transcriptome and bioinformatics analyses were conducted to uncover candidate molecules differentially expressed in patients with hematogenous recurrence of gastric cancer. One potential candidate identified was asialoglycoprotein receptor 2 (), and siRNA experiments were conducted to determine the effect of manipulating expression has on cell phenotypes. mRNA expression analysis using quantitative real-time reverse-transcription PCR was conducted with stage II/III gastric cancer clinical specimens ( = 95). Transcript levels were increased in gastric cancer cells as compared with a control nontumorigenic epithelial cell line. Knockdown of decreased the adhesion and migration potential. Thus, although gastric cancer cell-invasive activity was significantly decreased by knockdown, forced expression of promoted invasive activity. Using a mouse hepatic metastasis model, knockdown of resulted in the absence of hepatic metastasis formation. High expression in primary gastric cancer tissues was an independent predictor of shorter disease-free and overall survival. Finally, patients with high expression were more likely to have a high cumulative rate of hematogenous recurrence but not peritoneal or nodal recurrence. expression is associated with the malignant phenotypes in gastric cancer and represents a specific biomarker of hematogenous recurrences after curative resection for gastric cancer. .
血行转移复发是胃癌患者致死的主要原因,因此,需要寻找与血行转移复发相关的特异性生物标志物和潜在治疗靶点分子,以改善患者的预后。本研究通过转录组和生物信息学分析,发现了胃癌血行转移复发相关的差异表达基因。其中,唾液酸糖蛋白受体 2 () 是一个有潜力的候选基因,通过 siRNA 实验,研究了调控 表达对细胞表型的影响。采用实时定量逆转录 PCR 对 II/III 期胃癌临床标本(n = 95)进行 mRNA 表达分析。结果显示,与非肿瘤性上皮细胞系相比,胃癌细胞中 mRNA 水平升高。下调 表达可降低细胞黏附和迁移能力。尽管下调 可显著降低胃癌细胞的侵袭活性,但过表达 可促进侵袭活性。利用小鼠肝转移模型,下调 表达可导致肝转移形成缺失。在原发性胃癌组织中,高表达是无病生存和总生存时间较短的独立预测因素。最后,高表达患者发生血行复发的累积率较高,但腹膜或淋巴结复发率无差异。研究表明, 表达与胃癌的恶性表型相关,是胃癌根治术后血行转移复发的特异性生物标志物。