Coupling CDH17 and CLDN18 markers for comprehensive membrane-targeted detection of human gastric cancer.
Coupling CDH17 and CLDN18 markers for comprehensive membrane-targeted detection of human gastric cancer.
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DOI：
10.18632/oncotarget.11638
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发表时间：
2016-09-27
期刊：
影响因子：
--
通讯作者：
Fukayama M
中科院分区：
文献类型：
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作者：
Matsusaka K;Ushiku T;Urabe M;Fukuyo M;Abe H;Ishikawa S;Seto Y;Aburatani H;Hamakubo T;Kaneda A;Fukayama M
胃癌患者通常面临胃切除术，即使很少或没有淋巴结转移的报告。目前的程序预测淋巴转移很差，因此，评价癌细胞膜上表达的靶分子是体内检测所必需的。然而，标记物的开发受到胃癌细胞的肿瘤内异质性的限制。在这项研究中，42个系统性正常组织样本和56个胃癌样本的多基因表达阵列被用来研究两种粘附分子，钙粘蛋白17（CDH 17）和claudin 18（CLDN 18），这两种粘附分子分别是肠和胃的标志物。CDH 17和CLDN 18的表达部分重复，但在56例中有50例（89.3%）重叠。组织芯片构建的原发灶和淋巴结转移的106进展期胃癌显示，CDH 17和CLDN 18的表达在98例阳性（92%）。等级聚类将胃癌分为三个亚组，CDH 17（++）/CLDN 18（+/−）、CDH 17（++）/CLDN 18（++）或CDH 17（+）/CLDN 18（+）和CDH 17（−）/CLDN 18（++/+/−）。整个组织切片显示出对CDH 17和CLDN 18的强的、均匀的染色。总之，这些结果表明CDH 17和CLDN 18是有用的靶分子;此外，它们的偶联可以帮助体内胃癌转移的全面检测和定位，以克服与肿瘤内异质性相关的挑战。
Patients with gastric cancer typically face gastrectomies even when few or no nodal metastases are reported. Current procedures poorly predict lymphatic metastases; thus, evaluation of target molecules expressed on cancer cell membranes is necessary for in vivo detection. However, marker development is limited by the intratumoral heterogeneity of gastric cancer cells. In this study, multiple gene expression arrays of 42 systemic normal tissue samples and 56 gastric cancer samples were used to investigate two adhesion molecules, cadherin 17 (CDH17) and claudin 18 (CLDN18), which are intestinal and gastric markers, respectively. Expression of CDH17 and CLDN18 was partially redundant, but overlapped in 50 of 56 cases (89.3%). Tissue microarrays constructed using primary lesions and nodal metastases of 106 advanced gastric cancers revealed CDH17 and CLDN18 expression in 98 positive cases of 106 (92%). Hierarchical clustering classified gastric cancers into three subgroups, CDH17(++)/CLDN18(+/−), CDH17(++)/CLDN18(++) or CDH17(+)/CLDN18(+), and CDH17(−)/CLDN18(++/+/−). Whole tissue sections displayed strong, homogeneous staining for CDH17 and CLDN18. Together, these results indicate that CDH17 and CLDN18 are useful target molecules; moreover, their coupling can aid in the comprehensive detection and localization of gastric cancer metastases in vivo to overcome challenges associated with intratumoral heterogeneity.