Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
Ann Surg Oncol. 2012 Apr;19(4):1240-9. doi: 10.1245/s10434-011-2125-1. Epub 2011 Nov 3.
Our previous study indicated that gene expression profiling of intestinal metaplasia (IM) or spasmolytic polypeptide-expressing metaplasia (SPEM) can identify useful prognostic markers of early-stage gastric cancer, and seven metaplasia biomarkers (MUC13, CDH17, OLFM4, KRT20, LGALS4, MUC5AC, and REG4) were selectively expressed in 17-50% of gastric cancer tissues. We investigated whether the combined expression of these metaplasia biomarkers could predict the prognosis of advanced stage gastric cancer.
The expression of seven metaplasia biomarkers was evaluated immunohistochemically using tissue microarrays comprised of 450 gastric cancer patients. The clinicopathologic correlations and the prognostic impact were analyzed according to the expression of multiple biomarkers.
MUC13, CDH17, LGALS4, and REG4 were significant prognostic biomarkers in univariate analysis. No expression of four markers was found in 56 cases (14.2%); 1 marker was seen in 67 cases (17%), 2 in 106 cases (27%), 3 in 101 cases (25.7%), and 4 in 63 cases (16%). Patients in which two or fewer proteins were expressed (group B) showed younger age, undifferentiated or diffuse type cancer, larger tumor size, larger number of metastatic lymph nodes, and more advanced stage than those in which three or more proteins were expressed (group A). In undifferentiated or stage II/III gastric cancer, the prognosis of group B was significantly poorer than that of group A by multivariate analysis.
The combined loss of expression of multiple metaplasia biomarkers is considered an independent prognostic indicator in undifferentiated or stage II/III gastric cancer.
我们之前的研究表明，肠上皮化生（IM）或平滑肌多肽表达化生（SPEM）的基因表达谱可以识别早期胃癌的有用预后标志物，并且有七种化生生物标志物（MUC13、CDH17、OLFM4、KRT20、LGALS4、MUC5AC 和 REG4）选择性地在 17-50%的胃癌组织中表达。我们研究了这些化生生物标志物的联合表达是否可以预测晚期胃癌的预后。
使用包含 450 例胃癌患者的组织微阵列，通过免疫组织化学评估七种化生生物标志物的表达。根据多个标志物的表达分析了临床病理相关性和预后影响。
MUC13、CDH17、LGALS4 和 REG4 在单因素分析中是显著的预后生物标志物。在 56 例病例中未发现四种标志物的表达（14.2%）；在 67 例病例中发现 1 种标志物（17%），在 106 例病例中发现 2 种（27%），在 101 例病例中发现 3 种（25.7%），在 63 例病例中发现 4 种（16%）。与表达三种或更多种蛋白质的患者（A 组）相比，两种或更少蛋白质表达的患者（B 组）年龄较小，为未分化或弥漫型癌症，肿瘤较大，转移淋巴结较多，分期较晚。在未分化或 II/III 期胃癌中，B 组的预后明显比 A 组差。
多种化生生物标志物联合缺失表达被认为是未分化或 II/III 期胃癌的独立预后指标。
