CD44 variant 9 expression as a predictor for gastric cancer recurrence: immunohistochemical and metabolomic analysis of surgically resected tissues
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- YAMAKAWA Yushi
- Division of Colon and Rectal Surgery, Shizuoka Cancer Center Department of Surgery, School of Medicine, Keio University
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- KUSUHARA Masatoshi
- Regional Resources Division, Shizuoka Cancer Center Research Institute
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- TERASHIMA Masanori
- Division of Gastric Surgery, Shizuoka Cancer Center
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- KINUGASA Yusuke
- Division of Colon and Rectal Surgery, Shizuoka Cancer Center
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- SUGINO Takashi
- Division of Pathology, Shizuoka Cancer Center
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- ABE Masato
- Division of Pathology, Shizuoka Cancer Center
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- MOCHIZUKI Toru
- Medical Genetics Division, Shizuoka Cancer Center Research Institute
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- HATAKEYAMA Keiichi
- Medical Genetics Division, Shizuoka Cancer Center Research Institute
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- KAMI Kenjiro
- Human Metabolome Technologies, Inc., Tsuruoka
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- YAMAGUCHI Ken
- Shizuoka Cancer Center
書誌事項
- タイトル別名
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- <b>CD44 variant 9 expression as a predictor for gastric cancer recurrence: immunohistochemical and metabolomic analysis of surgically resected </b><b>tissues </b>
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抄録
<p>CD44 variant 9 (CD44v9) and the heavy chain of 4F2 cell-surface antigen (CD98hc) appear important for regulation of reactive oxygen species defence and tumor growth in gastric cancer. This study examined the roles of CD44v9 and CD98hc as markers of gastric cancer recurrence, and investigated associations with energy metabolism. We applied capillary electrophoresis time-of-flight mass spectrometry to metabolome profiling of gastric cancer specimens from 103 patients who underwent resection with no residual tumor or microscopic residual tumor, and compared metabolite levels to immunohistochemical staining for CD44v9 and CD98hc. Positive expression rates were 40.7% for CD44v9 and 42.7% for CD98hc. Various tumor characteristics were significantly associated with CD44v9 expression. Five-year recurrence-free survival rate was significantly lower for CD44v9-positive tumors (39.1%) than for CD44v9-negative tumors (73.5%; P < 0.0001), but no significant differences in recurrence-free survival were seen according to CD98hc expression. Uni- and multivariate analyses identified positive CD44v9 expression as an independent predictor of poorer recurrence-free survival. Metabolome analysis of 110 metabolites found that levels of glutathione disulfide were significantly lower and reduced glutathione (GSH)/ glutathione disulfide (GSSG) ratio was significantly higher in CD44v9-positive tumors than in CD44v9-negative tumors, suggesting that CD44v9 may enhance pentose phosphate pathway flux and maintain GSH levels in cancer cells.</p>
収録刊行物
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- Biomedical Research
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Biomedical Research 38 (1), 41-52, 2017
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