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Comparison of site-specific gene expression levels in primary tumors and synchronous lymph node metastases in advanced gastric cancer

Gastric Cancer, 2015, Vol.18(2), pp.262-270 [Peer Reviewed Journal]

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  • Title:
    Comparison of site-specific gene expression levels in primary tumors and synchronous lymph node metastases in advanced gastric cancer
  • Author: Naruke, Akira ; Azuma, Mizutomo ; Takeuchi, Atsuko ; Ishido, Kenji ; Katada, Chikatoshi ; Sasaki, Tohru ; Higuchi, Katsuhiko ; Tanabe, Satoshi ; Saegusa, Makoto ; Koizumi, Wasaburo
  • Found In: Gastric Cancer, 2015, Vol.18(2), pp.262-270 [Peer Reviewed Journal]
  • Subjects: Advanced gastric cancer ; Site-specific gene expression level ; Laser-captured microdissection
  • Language: English
  • Description: Byline: Akira Naruke (1), Mizutomo Azuma (1), Atsuko Takeuchi (1), Kenji Ishido (1), Chikatoshi Katada (1), Tohru Sasaki (1), Katsuhiko Higuchi (1), Satoshi Tanabe (1), Makoto Saegusa (2), Wasaburo Koizumi (1) Keywords: Advanced gastric cancer; Site-specific gene expression level; Laser-captured microdissection Abstract: Background Many malignant tumors consist of heterogeneous subpopulations of cells. This heterogeneity is associated with genetic characteristics. However, it remains unclear whether gene expression levels differ among specific sites of tumors in gastric cancer. Methods We studied differences in gene expression levels among specific sites of primary tumors and synchronous lymph node metastases, using formalin-fixed, paraffin-embedded specimens resected surgically from 48 patients with previously untreated advanced gastric cancer. Specimens were obtained by laser-captured microdissection from five regions: (1) nonneoplastic mucosa, (2) surface layer (mucosa) of the primary tumor (surface sections), (3) middle layer (submucosa) of the primary tumor (middle sections), (4) the deepest layer of the primary tumor (muscularis propria or deeper) at the site of deepest invasion (deep sections), and (5) level 1 synchronous lymph node metastasis (lymph node metastases). Expression levels of the following target genes were determined by quantitative real-time polymerase chain reaction: thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1[alpha] (HIF1[alpha]). Results TP, DPD, EGFR, and HIF1[alpha] gene expression levels were significantly higher in deep sections than in surface sections. TP, EGFR, VEGF, and HIF1[alpha] gene expression levels were significantly higher in lymph node metastases than in surface sections. TP, DPD, EGFR, VEGF, and HIF1[alpha] gene expression levels were positively correlated with the specific samples harvested from the tumors. Conclusions Our results show that the expression levels of some genes in tumor cells can change in specific sites of tumors and can become higher in association with tumor progression. Author Affiliation: (1) Department of Gastroenterology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan (2) Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan Article History: Registration Date: 20/02/2014 Received Date: 07/11/2013 Accepted Date: 08/02/2014 Online Date: 21/03/2014
  • Identifier: ISSN: 1436-3291 ; E-ISSN: 1436-3305 ; DOI: 10.1007/s10120-014-0357-z

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