Overexpression of RegIV in peritoneal dissemination of gastric cancer and its potential as A novel marker for the detection of peritoneal micrometastasis.
Overexpression of RegIV in peritoneal dissemination of gastric cancer and its potential as A novel marker for the detection of peritoneal micrometastasis.
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发表时间：
2008-03
影响因子：
2
通讯作者：
K. Miyagawa;C. Sakakura;S. Nakashima;T. Yoshikawa;K. Fukuda;S. Kin;Y. Nakase;K. Shimomura;N. Oue;W. Yasui;H. Hayasizaki;Y. Okazaki;H. Yamagishi;A. Hagiwara;E. Otsuji
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作者：
K. Miyagawa;C. Sakakura;S. Nakashima;T. Yoshikawa;K. Fukuda;S. Kin;Y. Nakase;K. Shimomura;N. Oue;W. Yasui;H. Hayasizaki;Y. Okazaki;H. Yamagishi;A. Hagiwara;E. Otsuji
再生基因IV型（RegIV）是癌症和炎症性肠病的候选标志物。在这项研究中，它作为一种新的标志物检测胃癌腹膜微转移的潜力进行了研究。患者和方法采用实时荧光定量RT-PCR技术检测95例胃癌患者和22例良性疾病患者腹腔冲洗液中RegIV mRNA水平。为了检查RegIV的表达是否增强致瘤性，将32只小鼠腹膜内或皮下注射TMK-1细胞的RegIV转染子、亲本TMK-1细胞或新霉素对照转染子。结果RegIV在腹膜转移患者中的表达明显高于无腹膜转移患者。胃癌患者中RegIV mRNA的表达水平与胃壁穿透程度有关。RegIV阳性表达的截止值基于对良性疾病阴性对照患者的分析，并且高于截止值的胃癌患者构成微转移（MM+）组。根据该标准，43例T1或T2病例中有3例为MM+（特异性93%）。在15例腹膜播散患者中（15例中有7例细胞学阳性），14例RegIV表达阳性（93%的敏感性），而癌胚抗原（CEA）mRNA分析未能检测到微转移的4例（73%的敏感性）。CEA与RegIV联合检测可提高诊断准确率达100%。RegIV阳性者预后明显差于RegIV阴性者。采用考克斯比例风险模型的多变量分析表明，RegIV可能是一个独立的预后因素。RegIV的稳定表达显著增强了胃癌动物模型的腹膜转移。结论RegIV mRNA表达有可能成为检测胃癌腹膜转移的新指标。
BACKGROUND Regenerating gene type IV (RegIV) is a candidate marker for cancer and inflammatory bowel disease. In this study, its potential as a novel marker for the detection of gastric cancer peritoneal micrometastases was examined. PATIENTS AND METHODS RegIV mRNA levels in the peritoneal washes of 95 gastric cancer patients and 22 with benign disease were quantified by real-time RT-PCR. To examine whether expression of RegIV enhance tumorigenicity or not, thirty two mice were injected intraperitoneally or subcutaneously with RegIV transfectants of TMK-1 cells, parental TMK-1 cells, or neomycin control transfectants. RESULTS RegIV expression was markedly higher in patients with peritoneal metastases compared to those without. The level of RegIV mRNA in gastric cancer patients was related to the extent of wall penetration. A cut-off value for RegIV-positive expression was based on an analysis of negative control patients with benign disease, and gastric cancer patients above the cut-off value constituted the micrometastasis (MM+) group. Based on this criteria, 3 out of 43 T1 or T2 cases were MM+ (93% specificity). Among 15 patients with peritoneal dissemination (7 out of 15 cases were positive by cytology), 14 cases were positive for RegIV expression (93% sensitivity), while analysis of carcinoembryonic antigen (CEA) mRNA failed to detect micrometastases in 4 cases (73% sensitivity). Combined analysis of CEA and RegIV improved the accuracy of diagnosis to 100%. The prognosis of RegIV-positive cases was significantly worse than that of RegIV-negative cases. Multivariate analysis using the Cox proportional hazards model suggested that RegIV may be an independent prognostic factor. Stable expression of RegIV significantly enhanced peritoneal metastasis in an animal model of gastric cancer. CONCLUSION These findings suggest that RegIV mRNA expression has the potential to serve as a novel marker for detecting peritoneal dissemination in gastric cancer.