Oue Naohide, Sentani Kazuhiro, Noguchi Tsuyoshi, Ohara Shinya, Sakamoto Naoya, Hayashi Tetsutaro, Anami Katsuhiro, Motoshita Junichi, Ito Masanori, Tanaka Shinji, Yoshida Kazuhiro, Yasui Wataru
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Int J Cancer. 2009 Nov 15;125(10):2383-92. doi: 10.1002/ijc.24624.
Gastric cancer (GC) is 1 of the most common human cancers. Early detection remains the most promising approach to improving long-term survival of patients with GC. We previously performed Serial Analysis of Gene Expression (SAGE) on 4 primary GCs and identified several GC-specific genes including Reg IV. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC-1) is a candidate gene for cancer-specific expression. In this study, we examined the expression of olfactomedin 4 in human GC by immunohistochemistry. We also assessed serum olfactomedin 4 levels in GC patients by enzyme-linked immunosorbent assay. 94 (56%) of 167 GC cases were positive for olfactomedin 4 by immunostaining. Olfactomedin 4 staining was observed more frequently in stage I/II cases than in stage III/IV cases. The serum olfactomedin 4 concentration in presurgical GC patients (n = 123, mean +/- SE, 36.3 +/- 3.5 ng/mL) was significantly higher than that in healthy individuals (n = 76, 16.6 +/- 1.6 ng/mL). In patients with stage I GC, the sensitivity of serum olfactomedin 4 (25%) and Reg IV (35%) was superior to that of CA19-9 (5%) or CEA (3%). Furthermore, in patients with stage I GC, the combination of olfactomedin 4 and Reg IV elevated the diagnostic sensitivity to 52%. These results suggest that serum olfactomedin 4 is a useful marker for GC and its measurement alone or in combination with Reg IV has utility in the early detection of GC.
胃癌(GC)是最常见的人类癌症之一。早期检测仍然是提高胃癌患者长期生存率最有前景的方法。我们之前对4例原发性胃癌进行了基因表达系列分析(SAGE),并鉴定出了几个胃癌特异性基因,包括Reg IV。在这些基因中,嗅觉介质4(OLFM4,也称为GW112或hGC-1)是癌症特异性表达的候选基因。在本研究中,我们通过免疫组织化学检测了嗅觉介质4在人胃癌中的表达。我们还通过酶联免疫吸附测定评估了胃癌患者血清中嗅觉介质4的水平。167例胃癌病例中有94例(56%)免疫染色显示嗅觉介质4呈阳性。在I/II期病例中比在III/IV期病例中更频繁地观察到嗅觉介质4染色。术前胃癌患者(n = 123,均值±标准误,36.3±3.5 ng/mL)血清嗅觉介质4浓度显著高于健康个体(n = 76,16.6±1.6 ng/mL)。在I期胃癌患者中,血清嗅觉介质4(25%)和Reg IV(35%)的敏感性优于CA19-9(5%)或癌胚抗原(CEA,3%)。此外,在I期胃癌患者中,嗅觉介质4和Reg IV联合使用可将诊断敏感性提高到52%。这些结果表明,血清嗅觉介质4是胃癌的一种有用标志物,单独检测或与Reg IV联合检测在胃癌的早期检测中具有实用价值。