Kanda Mitsuro, Shimizu Dai, Sueoka Satoshi, Nomoto Shuji, Oya Hisaharu, Takami Hideki, Ezaka Kazuhiro, Hashimoto Ryoji, Tanaka Yuri, Kobayashi Daisuke, Tanaka Chie, Yamada Suguru, Fujii Tsutomu, Nakayama Goro, Sugimoto Hiroyuki, Koike Masahiko, Fujiwara Michitaka, Kodera Yasuhiro
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Department of Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Aichi 464-8651, Japan.
Oncol Lett. 2016 Dec;12(6):4708-4716. doi: 10.3892/ol.2016.5233. Epub 2016 Oct 6.
The prognosis for patients with advanced gastric cancer (GC) remains poor. The identification of biomarkers relevant to the recurrence and metastasis of GC is advantageous for stratifying patients and proposing novel molecular targets. In the present study the oncological roles of SAM domain, SH3 domain and nuclear localization signals 1 (), a mediator of B-cell function, were elucidated in GC. The expression and methylation status of were investigated in a panel of 11 GC cell lines. Immunohistochemical staining was performed to determine the pattern of SAMSN1 protein expression in gastric tissues. The prognostic impact of expression was determined by analyzing 175 pairs of surgically resected gastric tissues. A marked decrease in the level of mRNA was detected in 8/11 GC cell lines as compared with that in a non-transformed intestinal epithelium cell line (FHs 74) without promoter methylation. The mean expression level of mRNA was reduced in GC tissues compared with normal adjacent tissues, an observation that was independent of tumor differentiation. The pattern of SAMSN1 protein expression was significantly correlated with that of mRNA. Low mRNA expression was significantly associated with tumor size (>60 mm; P=0.026) and shorter overall survival times (P=0.004). Multivariate analysis identified low mRNA expression as an independent prognostic factor for poor overall survival (hazard ratio, 1.80; 95% confidence interval, 1.07-3.05; P=0.025). The difference in survival between the low and high expression groups was more marked in patients with stage II/III GC compared to those with stage IV GC. In patients with stage II/III GC who underwent curative surgery, low expression was associated with reduced disease free survival times. The results of the present study indicate that downregulation of transcription may affect the progression and recurrence of GC, and therefore may represent a novel biomarker of GC.
晚期胃癌(GC)患者的预后仍然很差。鉴定与GC复发和转移相关的生物标志物有利于对患者进行分层并提出新的分子靶点。在本研究中,阐明了B细胞功能调节因子SAM结构域、SH3结构域和核定位信号1(SAMSN1)在GC中的肿瘤学作用。在一组11种GC细胞系中研究了SAMSN1的表达和甲基化状态。进行免疫组织化学染色以确定胃组织中SAMSN1蛋白的表达模式。通过分析175对手术切除的胃组织来确定SAMSN1表达的预后影响。与未发生启动子甲基化的未转化肠上皮细胞系(FHs 74)相比,在8/11的GC细胞系中检测到SAMSN1 mRNA水平显著降低。与相邻正常组织相比,GC组织中SAMSN1 mRNA的平均表达水平降低,这一观察结果与肿瘤分化无关。SAMSN1蛋白的表达模式与SAMSN1 mRNA的表达模式显著相关。低SAMSN1 mRNA表达与肿瘤大小(>60 mm;P = 0.026)和较短的总生存时间显著相关(P = 0.004)。多变量分析确定低SAMSN1 mRNA表达是总生存不良的独立预后因素(风险比,1.80;95%置信区间,1.07 - 3.05;P = 0.025)。与IV期GC患者相比,II/III期GC患者中低表达组和高表达组之间的生存差异更为明显。在接受根治性手术的II/III期GC患者中,低SAMSN1表达与无病生存时间缩短相关。本研究结果表明,SAMSN1转录下调可能影响GC的进展和复发,因此可能代表一种新的GC生物标志物。