Abstract
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.
Highlights
Gastric cancer is the third leading cause of cancerrelated death worldwide [1]
Whole tissue sections displayed strong, homogeneous staining for cadherin 17 (CDH17) and claudin 18 (CLDN18). These results indicate that CDH17 and CLDN18 are useful target molecules; their coupling can aid in the comprehensive detection and localization of gastric cancer metastases in vivo to overcome challenges associated with intratumoral heterogeneity
To further explore the relative expression patterns of CDH17, CLDN18, and CLDN7, hierarchical cluster analysis was performed on these genes in 56 gastric cancer cases (Figure 1E)
Summary
Gastrectomy with lymphadenectomy is a first-line choice for more complicated cases [2], nodal dissection often extends to non-metastatic lymph nodes [3]. These overtreatments are attributed to the absence of effective methods to detect cancer cells in vivo before or during an operation. Target molecules developed to detect metastases in vivo, such as in the intraoperative imaging method [4,5,6], could lead to limited operations and result in relief of complications after gastrectomy. Trastuzumab combined with chemotherapy was approved for HER2overexpressing gastric cancers, but the HER2 expression pattern is often not homogeneous, thwarting effective therapy [15, 17, 18]
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