S100A9, GIF and AAT as potential combinatorial biomarkers in gastric cancer diagnosis and prognosis

Abstract

Purpose: We have mined the gastric fluid proteome for potential gastric cancer (GC) biomarkers that may enhance disease detection and facilitate prognostic monitoring. Experimental design: In biomarker discovery, a total of 12 patient gastric fluid samples (stages I, III, IV and gastritis) were analysed by 2DE for expression changes that correlated with GC status or disease progression. Gastric fluid proteins showing differential expression with GC were identified by MALDI-TOF/TOF MS as putative biomarkers. Levels of these potential biomarker candidates were independently validated by Western blotting in further 60 gastritis and GC patients. A targeted approach that recruits biomarker candidates for panel consideration was adopted to test if two or more biomarkers in combination improved diagnostic power. Results: From the 15 differentially regulated proteins identified, expression levels of S100A9, GIF and AAT in the gastric fluid clearly correlated with GC status. S100A9/AAT (AUC = 0.81) and S100A9/GIF (AUC = 0.92) were revealed as promising biomarker pairs for early GC diagnosis and disease monitoring, respectively. Conclusion and clinical relevance: Early diagnosis, accurate staging and constant disease monitoring remain the prerequisites for effective treatment against GC. As current biomarkers like CA19-9 and carcinoembryonic antigen (CEA) lack sensitivity and specificity, there is a pressing need for novel GC detection and monitoring methods. To this end, S100A9, GIF and AAT from the gastric fluid may significantly augment existing methods of GC detection and monitoring, and eliminate the need for invasive tissue biopsies. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.