DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection

Hiromichi Miyagaki, Makoto Yamasaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Hiroshi Miyata, Kiyokazu Nakajima, Shuji Takiguchi, Yoshiyuki Fujiwara, Masaki Mori, Yuichiro Doki

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Abstract

Background. DOK2 is known as the substrate of chmeric p210bcr/abl oncoprotein characterizing chronic myelogenous leukemia with Philadelphia chromosome. Reduced DOK2 expression was recently reported in lung adenocarcinoma, suggesting that this protein acts as a tumor suppressor in solid tumors. The purpose of this study was to determine the significance of DOK2 in gastric cancer. Methods. The study subjects were 118 patients who underwent curative surgery for gastric cancer, as well as 7 gastric cancer cell lines. The tissues and cell lines were analyzed for DOK2 gene and protein expressions by histopathology and immunohistochemistry, and also using a microsatellite marker for loss of heterozygosity. Correlation of survival with clinicopathological parameters was investigated by univariate and multivariate analyses. Results. DOK2 expression was confirmed in the normal gastric mucosa. Considerable differences in the gene expression were noted among the gastric cell lines. Positive DOK2 expression was noted in the noncancerous regions of all pathological specimens, whereas 59 (50.0%) specimens of 118 patients were negatively stained in the tumor. Loss of heterozygosity was observed in 54.5% of DOK2(-) cases. DOK2(-) patients were more likely to develop recurrence than DOK2(+) and showed poorer 5-year overall survival (59.1%) than DOK2(+) (76.4%, P = .0403). Multivariate analysis identified pT (hazard ratio [HR] = 2.748, 95% confidence interval [95% CI] = 1.061-8.927, P = .0361), pN (HR = 2.486, 95% CI = 1.264-4.932, P = .0086), and DOK2(-) (HR = 2.343, 95% CI = 1.211-4.727, P = .0112) as significant and independent determinants of poor survival. Conclusions. Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative resection.

Original languageEnglish
Pages (from-to)1560-1567
Number of pages8
JournalAnnals of Surgical Oncology
Volume19
Issue number5
DOIs
Publication statusPublished - May 1 2012
Externally publishedYes

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Stomach Neoplasms
Stomach
Adenocarcinoma
Loss of Heterozygosity
Confidence Intervals
Cell Line
Survival
Multivariate Analysis
Gene Expression
Philadelphia Chromosome
Neoplasms
Oncogene Proteins
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Gastric Mucosa
Microsatellite Repeats
Proteins
Immunohistochemistry
Recurrence

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Miyagaki, H., Yamasaki, M., Takahashi, T., Kurokawa, Y., Miyata, H., Nakajima, K., ... Doki, Y. (2012). DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection. Annals of Surgical Oncology, 19(5), 1560-1567. https://doi.org/10.1245/s10434-011-2157-6

DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection. / Miyagaki, Hiromichi; Yamasaki, Makoto; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Miyata, Hiroshi; Nakajima, Kiyokazu; Takiguchi, Shuji; Fujiwara, Yoshiyuki; Mori, Masaki; Doki, Yuichiro.

In: Annals of Surgical Oncology, Vol. 19, No. 5, 01.05.2012, p. 1560-1567.

Research output: Contribution to journalArticle

Miyagaki, H, Yamasaki, M, Takahashi, T, Kurokawa, Y, Miyata, H, Nakajima, K, Takiguchi, S, Fujiwara, Y, Mori, M & Doki, Y 2012, 'DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection', Annals of Surgical Oncology, vol. 19, no. 5, pp. 1560-1567. https://doi.org/10.1245/s10434-011-2157-6
Miyagaki, Hiromichi ; Yamasaki, Makoto ; Takahashi, Tsuyoshi ; Kurokawa, Yukinori ; Miyata, Hiroshi ; Nakajima, Kiyokazu ; Takiguchi, Shuji ; Fujiwara, Yoshiyuki ; Mori, Masaki ; Doki, Yuichiro. / DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection. In: Annals of Surgical Oncology. 2012 ; Vol. 19, No. 5. pp. 1560-1567.
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abstract = "Background. DOK2 is known as the substrate of chmeric p210bcr/abl oncoprotein characterizing chronic myelogenous leukemia with Philadelphia chromosome. Reduced DOK2 expression was recently reported in lung adenocarcinoma, suggesting that this protein acts as a tumor suppressor in solid tumors. The purpose of this study was to determine the significance of DOK2 in gastric cancer. Methods. The study subjects were 118 patients who underwent curative surgery for gastric cancer, as well as 7 gastric cancer cell lines. The tissues and cell lines were analyzed for DOK2 gene and protein expressions by histopathology and immunohistochemistry, and also using a microsatellite marker for loss of heterozygosity. Correlation of survival with clinicopathological parameters was investigated by univariate and multivariate analyses. Results. DOK2 expression was confirmed in the normal gastric mucosa. Considerable differences in the gene expression were noted among the gastric cell lines. Positive DOK2 expression was noted in the noncancerous regions of all pathological specimens, whereas 59 (50.0{\%}) specimens of 118 patients were negatively stained in the tumor. Loss of heterozygosity was observed in 54.5{\%} of DOK2(-) cases. DOK2(-) patients were more likely to develop recurrence than DOK2(+) and showed poorer 5-year overall survival (59.1{\%}) than DOK2(+) (76.4{\%}, P = .0403). Multivariate analysis identified pT (hazard ratio [HR] = 2.748, 95{\%} confidence interval [95{\%} CI] = 1.061-8.927, P = .0361), pN (HR = 2.486, 95{\%} CI = 1.264-4.932, P = .0086), and DOK2(-) (HR = 2.343, 95{\%} CI = 1.211-4.727, P = .0112) as significant and independent determinants of poor survival. Conclusions. Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative resection.",
author = "Hiromichi Miyagaki and Makoto Yamasaki and Tsuyoshi Takahashi and Yukinori Kurokawa and Hiroshi Miyata and Kiyokazu Nakajima and Shuji Takiguchi and Yoshiyuki Fujiwara and Masaki Mori and Yuichiro Doki",
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T1 - DOK2 as a marker of poor prognosis of patients with gastric adenocarcinoma after curative resection

AU - Miyagaki, Hiromichi

AU - Yamasaki, Makoto

AU - Takahashi, Tsuyoshi

AU - Kurokawa, Yukinori

AU - Miyata, Hiroshi

AU - Nakajima, Kiyokazu

AU - Takiguchi, Shuji

AU - Fujiwara, Yoshiyuki

AU - Mori, Masaki

AU - Doki, Yuichiro

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N2 - Background. DOK2 is known as the substrate of chmeric p210bcr/abl oncoprotein characterizing chronic myelogenous leukemia with Philadelphia chromosome. Reduced DOK2 expression was recently reported in lung adenocarcinoma, suggesting that this protein acts as a tumor suppressor in solid tumors. The purpose of this study was to determine the significance of DOK2 in gastric cancer. Methods. The study subjects were 118 patients who underwent curative surgery for gastric cancer, as well as 7 gastric cancer cell lines. The tissues and cell lines were analyzed for DOK2 gene and protein expressions by histopathology and immunohistochemistry, and also using a microsatellite marker for loss of heterozygosity. Correlation of survival with clinicopathological parameters was investigated by univariate and multivariate analyses. Results. DOK2 expression was confirmed in the normal gastric mucosa. Considerable differences in the gene expression were noted among the gastric cell lines. Positive DOK2 expression was noted in the noncancerous regions of all pathological specimens, whereas 59 (50.0%) specimens of 118 patients were negatively stained in the tumor. Loss of heterozygosity was observed in 54.5% of DOK2(-) cases. DOK2(-) patients were more likely to develop recurrence than DOK2(+) and showed poorer 5-year overall survival (59.1%) than DOK2(+) (76.4%, P = .0403). Multivariate analysis identified pT (hazard ratio [HR] = 2.748, 95% confidence interval [95% CI] = 1.061-8.927, P = .0361), pN (HR = 2.486, 95% CI = 1.264-4.932, P = .0086), and DOK2(-) (HR = 2.343, 95% CI = 1.211-4.727, P = .0112) as significant and independent determinants of poor survival. Conclusions. Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative resection.

AB - Background. DOK2 is known as the substrate of chmeric p210bcr/abl oncoprotein characterizing chronic myelogenous leukemia with Philadelphia chromosome. Reduced DOK2 expression was recently reported in lung adenocarcinoma, suggesting that this protein acts as a tumor suppressor in solid tumors. The purpose of this study was to determine the significance of DOK2 in gastric cancer. Methods. The study subjects were 118 patients who underwent curative surgery for gastric cancer, as well as 7 gastric cancer cell lines. The tissues and cell lines were analyzed for DOK2 gene and protein expressions by histopathology and immunohistochemistry, and also using a microsatellite marker for loss of heterozygosity. Correlation of survival with clinicopathological parameters was investigated by univariate and multivariate analyses. Results. DOK2 expression was confirmed in the normal gastric mucosa. Considerable differences in the gene expression were noted among the gastric cell lines. Positive DOK2 expression was noted in the noncancerous regions of all pathological specimens, whereas 59 (50.0%) specimens of 118 patients were negatively stained in the tumor. Loss of heterozygosity was observed in 54.5% of DOK2(-) cases. DOK2(-) patients were more likely to develop recurrence than DOK2(+) and showed poorer 5-year overall survival (59.1%) than DOK2(+) (76.4%, P = .0403). Multivariate analysis identified pT (hazard ratio [HR] = 2.748, 95% confidence interval [95% CI] = 1.061-8.927, P = .0361), pN (HR = 2.486, 95% CI = 1.264-4.932, P = .0086), and DOK2(-) (HR = 2.343, 95% CI = 1.211-4.727, P = .0112) as significant and independent determinants of poor survival. Conclusions. Our data suggest the potential usefulness of DOK2 as a marker of poor prognosis in patients with gastric cancer after curative resection.

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