Basic—Alimentary TractGene Expression Profiling of Metaplastic Lineages Identifies CDH17 as a Prognostic Marker in Early Stage Gastric Cancer
Section snippets
Oligonucleotide Microarray From Microdissected RNA
Total RNAs from both IM and SPEM lineages adjacent to intestinal-type gastric cancer in fundus were collected from 6 patients who underwent gastrectomy. In addition, because transdifferentiation of chief cells into SPEM appears to be the first step in metaplastic response to oxyntic atrophy, RNAs from normal chief cells were collected from 6 patients who underwent gastrectomy with no evidence of atrophic gastritis, IM, SPEM, or gastric cancer in the fundic mucosa. All samples were obtained from
Gene Expression Profile of SPEM and IM Compared With Normal Chief Cells
Based on our recent studies indicating that SPEM is derived from chief cells in mice,15, 16 we sought to compare the expression profiles for microdissected IM and SPEM compared with normal chief cells. We identified 858 probes, which were differentially expressed between chief cells vs IM or SPEM. Among them, 45 probes were significantly up-regulated in both SPEM and IM, 523 were significantly up-regulated in IM alone, 287 were significantly down-regulated in IM alone, and 3 were significantly
Discussion
Perioperative or postoperative chemotherapy is generally recommended for the treatment of advanced gastric cancer.3, 29 However, for stage I gastric cancer, which has a 20%–30% 5-year recurrence rate, appropriate criteria for adjuvant chemotherapy have not been available. In contrast, in the early stage, for node-negative breast cancer, a number of prognostic markers are used in the clinical setting to select candidates for adjuvant treatment.30 The results in the present investigation suggest
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants from NIHRO1 DK071590, a pilot project grant from the Vanderbilt SPORE in Gastrointestinal Cancer (P50 CA95103), the AGA Funderburg Award in Gastric Biology Related to Cancer, a Department of Veterans Affairs Merit Review Award and a Discovery Grant from the Vanderbilt-Ingram Cancer Center (to J.R.G.); by grants from the Cancer Research Institute, Seoul National University (CRI-09-3), and the Seoul National University Hospital Research Fund (05-2009-002) (to H.J.L.); and, for the microarray studies performed in the Vanderbilt Microarray Core Facility, by the Vanderbilt Ingram Cancer Center (P30 CA68485) and the Vanderbilt Digestive Disease Research Center (DK058404).