Nuclear expression of N-myc downstream regulated gene 1/ Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer

Akihiko Kawahara, Jun Akiba, Satoshi Hattori, Tomohiko Yamaguchi, Hideyuki Abe, Tomoki Taira, Hiroki Ureshino, Yuichi Murakami, Kosuke Watari, Kikuo Koufuji, Kazuo Shirouzu, Michihiko Kuwano, Mayumi Ono, Masayoshi Kages

Research output: Contribution to journalArticle

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Abstract

Expression of N-myc downstream regulated gene 1 (NDRG1)/Ca2+-associated protein 43 (Cap43) in cancer cells is a predictive marker of good or poor prognosis depending on tumor type. In this study, we examined whether NDRG1/ Cap43 is a marker of good or poor prognosis in gastric cancer patients, and whether it is associated with tumor stromal responses, including angiogenesis and macrophage infiltration. The expression levels of NDRG1/Cap43, the number of CD68- positive macrophages and the CD34-positive microvessel density were analyzed by immunohistochemistry in 129 gastric cancer patients, including 65 with the intestinal type and 64 with the diffuse type. The expression of NDRG1/Cap43 in the nucleus and the membrane was evaluated. Nuclear NDRG1/ Cap43 expression was found in 20/65 (30.8%) patients with the intestinal type and in 9/64 (14.1%) patients with the diffuse type of gastric cancer. Nuclear NDRG1/Cap43 expression was significantly associated with pathological stage in the intestinal type (P=0.002), but not in the diffuse type (P=0.039). Nuclear NDRG1/Cap43 expression was also closely associated with infiltrating macrophages (P=0.001) and tumor angiogenesis (P=0.001) in the intestinal type. Furthermore, nuclear NDRG1/Cap43 expression was associated with poor prognosis in both the intestinal (P=0.001) and the diffuse types of gastric cancer (P=0.047). By contrast, membranous NDRG1/ Cap43 expression was not associated with the overall survival of gastric cancer patients with either the intestinal or diffuse type of gastric cancer. The expression of NDRG1/cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of NDRG1/Cap43 in the membrane.

Original languageEnglish
Pages (from-to)471-479
Number of pages9
JournalExperimental and Therapeutic Medicine
Volume2
Issue number3
DOIs
Publication statusPublished - May 1 2011
Externally publishedYes

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Stomach Neoplasms
Survival
Genes
Neoplasms
Proteins
Macrophages
Intestinal Neoplasms
Membranes
Microvessels
Biomarkers
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

Cite this

Nuclear expression of N-myc downstream regulated gene 1/ Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer. / Kawahara, Akihiko; Akiba, Jun; Hattori, Satoshi; Yamaguchi, Tomohiko; Abe, Hideyuki; Taira, Tomoki; Ureshino, Hiroki; Murakami, Yuichi; Watari, Kosuke; Koufuji, Kikuo; Shirouzu, Kazuo; Kuwano, Michihiko; Ono, Mayumi; Kages, Masayoshi.

In: Experimental and Therapeutic Medicine, Vol. 2, No. 3, 01.05.2011, p. 471-479.

Research output: Contribution to journalArticle

Kawahara, A, Akiba, J, Hattori, S, Yamaguchi, T, Abe, H, Taira, T, Ureshino, H, Murakami, Y, Watari, K, Koufuji, K, Shirouzu, K, Kuwano, M, Ono, M & Kages, M 2011, 'Nuclear expression of N-myc downstream regulated gene 1/ Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer', Experimental and Therapeutic Medicine, vol. 2, no. 3, pp. 471-479. https://doi.org/10.3892/etm.2011.222
Kawahara, Akihiko ; Akiba, Jun ; Hattori, Satoshi ; Yamaguchi, Tomohiko ; Abe, Hideyuki ; Taira, Tomoki ; Ureshino, Hiroki ; Murakami, Yuichi ; Watari, Kosuke ; Koufuji, Kikuo ; Shirouzu, Kazuo ; Kuwano, Michihiko ; Ono, Mayumi ; Kages, Masayoshi. / Nuclear expression of N-myc downstream regulated gene 1/ Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer. In: Experimental and Therapeutic Medicine. 2011 ; Vol. 2, No. 3. pp. 471-479.
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abstract = "Expression of N-myc downstream regulated gene 1 (NDRG1)/Ca2+-associated protein 43 (Cap43) in cancer cells is a predictive marker of good or poor prognosis depending on tumor type. In this study, we examined whether NDRG1/ Cap43 is a marker of good or poor prognosis in gastric cancer patients, and whether it is associated with tumor stromal responses, including angiogenesis and macrophage infiltration. The expression levels of NDRG1/Cap43, the number of CD68- positive macrophages and the CD34-positive microvessel density were analyzed by immunohistochemistry in 129 gastric cancer patients, including 65 with the intestinal type and 64 with the diffuse type. The expression of NDRG1/Cap43 in the nucleus and the membrane was evaluated. Nuclear NDRG1/ Cap43 expression was found in 20/65 (30.8{\%}) patients with the intestinal type and in 9/64 (14.1{\%}) patients with the diffuse type of gastric cancer. Nuclear NDRG1/Cap43 expression was significantly associated with pathological stage in the intestinal type (P=0.002), but not in the diffuse type (P=0.039). Nuclear NDRG1/Cap43 expression was also closely associated with infiltrating macrophages (P=0.001) and tumor angiogenesis (P=0.001) in the intestinal type. Furthermore, nuclear NDRG1/Cap43 expression was associated with poor prognosis in both the intestinal (P=0.001) and the diffuse types of gastric cancer (P=0.047). By contrast, membranous NDRG1/ Cap43 expression was not associated with the overall survival of gastric cancer patients with either the intestinal or diffuse type of gastric cancer. The expression of NDRG1/cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of NDRG1/Cap43 in the membrane.",
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AU - Hattori, Satoshi

AU - Yamaguchi, Tomohiko

AU - Abe, Hideyuki

AU - Taira, Tomoki

AU - Ureshino, Hiroki

AU - Murakami, Yuichi

AU - Watari, Kosuke

AU - Koufuji, Kikuo

AU - Shirouzu, Kazuo

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AU - Ono, Mayumi

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N2 - Expression of N-myc downstream regulated gene 1 (NDRG1)/Ca2+-associated protein 43 (Cap43) in cancer cells is a predictive marker of good or poor prognosis depending on tumor type. In this study, we examined whether NDRG1/ Cap43 is a marker of good or poor prognosis in gastric cancer patients, and whether it is associated with tumor stromal responses, including angiogenesis and macrophage infiltration. The expression levels of NDRG1/Cap43, the number of CD68- positive macrophages and the CD34-positive microvessel density were analyzed by immunohistochemistry in 129 gastric cancer patients, including 65 with the intestinal type and 64 with the diffuse type. The expression of NDRG1/Cap43 in the nucleus and the membrane was evaluated. Nuclear NDRG1/ Cap43 expression was found in 20/65 (30.8%) patients with the intestinal type and in 9/64 (14.1%) patients with the diffuse type of gastric cancer. Nuclear NDRG1/Cap43 expression was significantly associated with pathological stage in the intestinal type (P=0.002), but not in the diffuse type (P=0.039). Nuclear NDRG1/Cap43 expression was also closely associated with infiltrating macrophages (P=0.001) and tumor angiogenesis (P=0.001) in the intestinal type. Furthermore, nuclear NDRG1/Cap43 expression was associated with poor prognosis in both the intestinal (P=0.001) and the diffuse types of gastric cancer (P=0.047). By contrast, membranous NDRG1/ Cap43 expression was not associated with the overall survival of gastric cancer patients with either the intestinal or diffuse type of gastric cancer. The expression of NDRG1/cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of NDRG1/Cap43 in the membrane.

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