NM23/nucleoside diphosphate kinase-A as a potent prognostic marker in invasive pancreatic ductal carcinoma identified by proteomic analysis of laser micro-dissected formalin-fixed paraffin-embedded tissue

Tatsuyuki Takadate, Tohru Onogawa, Kiyonaga Fujii, Fuyuhiko Motoi, Sayaka Mikami, Tetsuya Fukuda, Makoto Kihara, Takashi Suzuki, Taro Takemura, Takashi Minowa, Nobutaka Hanagata, Kengo Kinoshita, Takanori Morikawa, Keiichi Shirasaki, Toshiki Rikiyama, Yu Katayose, Shinichi Egawa, Toshihide Nishimura, Michiaki Unno

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Background: Pancreatic cancer is among the most lethal malignancies worldwide. This study aimed to identify a novel prognostic biomarker, facilitating treatment selection, using mass spectrometry (MS)-based proteomic analysis with formalin-fixed paraffin-embedded (FFPE) tissue. Results: The two groups with poor prognosis (n = 4) and with better prognosis (n = 4) had been carefully chosen among 96 resected cases of pancreatic cancer during 1998 to 2007 in Tohoku University Hospital. Although those 2 groups had adjusted background (UICC-Stage IIB, Grade2, R0, gemcitabine adjuvant), there was a significant difference in postoperative mean survival time (poor 21.0 months, better 58.1 months, P = 0.0067). Cancerous epithelial cells collected from FFPE tissue sections by laser micro-dissection (LMD) were processed for liquid chromatography-tandem mass spectrometry (LC-MS/MS). In total, 1099 unique proteins were identified and 6 proteins showed different expressions in the 2 groups by semi-quantitative comparison. Among these 6 proteins, we focused on Nm23/Nucleoside Diphosphate Kinase A (NDPK-A) and immunohistochemically confirmed its expression in the cohort of 96 cases. Kaplan-Meier analysis showed high Nm23/NDPK-A expression to correlate with significantly worse overall survival (ρ = 0.0103). Moreover, in the multivariate Cox regression model, Nm23/NDPK-A over-expression remained an independent predictor of poor survival with a hazard ratio of 1.97 (95% CI 1.16-3.56, ρ = 0.0110). Conclusions: We identified 6 candidate prognostic markers for postoperative pancreatic cancer using FFPE tissues and immunohistochemically demonstrated high Nm23/NDPK-A expression to be a useful prognostic marker for pancreatic cancer.

Original languageEnglish
Article number8
JournalClinical Proteomics
Volume9
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • Formalin-fixed paraffin-embedded (FFPE)
  • Laser micro-dissection (LMD)
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
  • Nm23/nucleoside diphosphate kinase a (NDPK-A)
  • Prognostic biomarker
  • Proteomics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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