Discovery and validation of an INflammatory PROtein-driven GAstric cancer Signature (INPROGAS) using antibody microarray-based oncoproteomics
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Manuel Puig-Costa1,2, Antonio Codina-Cazador1,2, Elisabet Cortés-Pastoret2,3, Cristina Oliveras-Ferraros2,3, Sílvia Cufí2,3, Sílvia Flaquer2,4, Francesca Llopis-Puigmarti2,4, Eulalia Pujol-Amado2,4, Bruna Corominas-Faja2,3, Elisabet Cuyàs2,3, Rosa Ortiz5, Eugeni Lopez-Bonet5, Bernardo Queralt6, Raquel Guardeño6, Begoña Martin-Castillo2,4, Josep Roig1,2, Jorge Joven7, Javier A. Menendez2,3
1 Department of General and Digestive Surgery, Dr. Josep Trueta University Hospital, Catalonia, Spain
2 Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain
3 Metabolism & Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology, Girona, Catalonia, Spain
4 Unit of Clinical Research, Catalan Institute of Oncology, Girona, Catalonia, Spain
5 Department of Anatomical Pathology, Dr. Josep Trueta University Hospital, Girona, Catalonia, Spain
6 Medical Oncology, Catalan Institute of Oncology, Girona, Catalonia, Spain
7 Unitat de Recerca Biomèdica (URB-CRB), Institut d’Investigació Sanitaria Pere i Virgili (IISPV), Universitat Rovira i Virgili; Reus, Catalonia, Spain
Javier A. Menendez, email:
Keywords: Gastric cancer, inflammation, antibody arrays, cytokines, angiogenesis
Received: February 14, 2014 Accepted: March 31, 2014 Published: March 31, 2014
This study aimed to improve gastric cancer (GC) diagnosis by identifying and validating an INflammatory PROtein-driven GAstric cancer Signature (hereafter INPROGAS) using low-cost affinity proteomics. The detection of 120 cytokines, 43 angiogenic factors, 41 growth factors, 40 inflammatory factors and 10 metalloproteinases was performed using commercially available human antibody microarray-based arrays. We identified 21 inflammation-related proteins (INPROGAS) with significant differences in expression between GC tissues and normal gastric mucosa in a discovery cohort of matched pairs (n=10) of tumor/normal gastric tissues. Ingenuity pathway analysis confirmed the “inflammatory response”, “cellular movement” and “immune cell trafficking” as the most overrepresented biofunctions within INPROGAS. Using an expanded independent validation cohort (n = 22), INPROGAS classified gastric samples as “GC” or “non-GC” with a sensitivity of 82% (95% CI 59-94) and a specificity of 73% (95% CI 49-89). The positive predictive value and negative predictive value in this validation cohort were 75% (95% CI 53-90) and 80% (95% CI 56-94), respectively. The positive predictive value and negative predictive value in this validation cohort were 75% (95% CI 53-90) and 80% (95% CI 56-94), respectively. Antibody microarray analyses of the GC-associated inflammatory proteome identified a 21-protein INPROGAS that accurately discriminated GC from noncancerous gastric mucosa.
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