Clinical Proteomics (Jun 2012)

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

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

DOI
https://doi.org/10.1186/1559-0275-9-8
Journal volume & issue
Vol. 9, no. 1
p. 8

Abstract

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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 (P = 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, P = 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.

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