Discovery and validation of an INflammatory PROtein-driven GAstric cancer Signature (INPROGAS) using antibody microarray-based oncoproteomics.
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.
Department of General and Digestive Surgery, Dr. Josep Trueta University Hospital, Catalonia, Spain.
Manuel
M
Puig-Costa
Antonio
A
Codina-Cazador
Elisabet
E
Cortés-Pastoret
Cristina
C
Oliveras-Ferraros
Sílvia
S
Cufí
Sílvia
S
Flaquer
Francesca
F
Llopis-Puigmarti
Eulalia
E
Pujol-Amado
Bruna
B
Corominas-Faja
Elisabet
E
Cuyàs
Rosa
R
Ortiz
Eugeni
E
Lopez-Bonet
Bernardo
B
Queralt
Raquel
R
Guardeño
Begoña
B
Martin-Castillo
Josep
J
Roig
Jorge
J
Joven
Javier A
JA
Menendez
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism*; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation / Q000378:metabolism; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D008875:Middle Aged; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D040901:Proteomics; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D016207:Cytokines; D045726:Metalloproteases