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
1 Division of Gastroenterological Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Miyagi, Japan
2 Department of Structural Biology, Hokkaido University Graduate School of Pharmaceutical Sciences, Sapporo, Japan
3 Biosys Technologies, Incorporated, Tokyo, Japan
4 Medical ProteoScope Company, Limited, Kanagawa, Japan
5 Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan
6 Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Japan
7 Department of Applied Information Sciences, Tohoku University Graduate School of Information Science, Sendai, Japan
8 Division of Integrated Surgery and Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
9 Department of Surgery I, Tokyo Medical University, Tokyo, Japan
Clinical Proteomics 2012, 9:8 doi:10.1186/1559-0275-9-8Published: 27 June 2012
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.
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).
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.