Paraneoplastic Ma Antigen-Like 1 as a Potential Prognostic Biomarker in Human Pancreatic Ductal Adenocarcinoma.

ABSTRACT

OBJECTIVE: The present study aimed to identify novel useful clinical biomarker at early stages and to elucidate the molecular background of carcinogenesis in human pancreatic ductal adenocarcinomas (PDACs). METHODS: Proteomes of dissected PDACs and adjacent nontumor pancreatic tissues from formalin-fixed and paraffin-embedded sections from 10 patients were analyzed using QSTAR Elite liquid chromatography-tandem mass spectrometry, ProteinPilot Software, and Ingenuity Pathway Analysis. Expression of potential biomarker candidates was validated immunohistochemically in 50 PDAC patients, followed by survival analyses and statistical comparison of protein expression with clinicopathologic variables. RESULTS: Eight hundred five proteins displaying significant quantitative changes were identified in human PDACs by liquid chromatography-tandem mass spectrometry. Based on altered expression of downstream molecules, Ingenuity Pathway Analysis predicted up-regulation and/or activation of nuclear factor ß-catenin, SOX11, enolase 1, NFE2L2, SP1, SMAD1, SMAD2, SMAD3, SMAD4, HIF-1, and others. From proteome analysis, paraneoplastic Ma antigen-like 1 was selected as a potential biomarker of human PDAC. Furthermore, paraneoplastic neuronal Ma antigen-like 1 immunohistochemical evaluation in 50 PDAC patients revealed that its positive expression was significantly associated with the better overall survival (log-rank test; P = 0.009) and histological differentiation of PDACs (well, moderate, and poor; P = 0.027) as compared with patients with negative expression. CONCLUSION: Paraneoplastic Ma antigen-like 1 is suggested as a novel potential clinically useful prognostic biomarker for patients with PDAC.