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DOK2 as a Marker of Poor Prognosis of Patients with Gastric Adenocarcinoma After Curative Resection

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Disclosures

Hiromichi Miyagaki and all authors of the manuscript: “Evaluation of DOK2 protein expression in gastric adenocarcinoma” declare no conflict of interest and no financial ties to disclose.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

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

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  1. Hiromichi Miyagaki MD
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  2. Makoto Yamasaki MD, PhD
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  5. Hiroshi Miyata MD, PhD
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  10. Yuichiro Doki MD, PhD
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Correspondence to Makoto Yamasaki MD, PhD.

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10434_2011_2157_MOESM1_ESM.eps

Supplementary Figure 1. DOK genes expression in gastric mucosa and gastric cancer cell lines determined by RT-PCR. a Normal gastric mucosa cells were collected using laser microdissection. The expression of DOK1 and DOK2, but not DOK3, was evident in all normal gastric mucosa samples. The cDNA from peripheral mononuclear blood cells was used as a positive control. b In gastric cancer cell lines, DOK1 mRNA expression was observed in all gastric cancer cell line, while DOK3 mRNA expression was hardly observed. DOK2 expression was strong in MKN7 and AGS, weak in MKN74, and negative in MKN45, MKN45P, NUGC3, and RERFGC1B β2-microglobulin (B2M) was used as a control gene. (EPS 3,067 kb)

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Miyagaki, H., Yamasaki, M., Takahashi, T. et al. DOK2 as a Marker of Poor Prognosis of Patients with Gastric Adenocarcinoma After Curative Resection. Ann Surg Oncol 19, 1560–1567 (2012). https://doi.org/10.1245/s10434-011-2157-6

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  • DOI: https://doi.org/10.1245/s10434-011-2157-6

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