Clinical implications and diagnostic usefulness of correlation between soluble major histocompatibility complex class I chain-related molecule a and protumorigenic cytokines in pancreatic ductal adenocarcinoma.
BACKGROUND
Tumor-derived soluble factors serve as mediators between tumors and surrounding microenvironment to promote tumor growth and metastasis under a complex network. The objective of this study was to evaluate the relationships between soluble major histocompatibility complex class I chain-related molecule A (sMICA) and 4 categories of cytokines (tumor-related proinflammatory, anti-inflammatory, chemotactic/proangiogenic, and growth-stimulatory) in the development and progression of pancreatic ductal adenocarcinoma (PDAC).


METHODS
Serum levels of sMICA and 4-categorized cytokines were measured by enzyme-linked immunosorbent assay and chemiluminescent immunoassay, respectively, in 134 individuals (normal, n = 55; chronic pancreatitis, n = 25; PDAC, n = 54). Clinical implications of sMICA and tumor-related cytokines, their correlations, and diagnostic usefulness in PDAC were evaluated.


RESULTS
Serum sMICA, which was associated with the development and progression of PDAC, correlated with interferon-γ negatively (P = 0.024), whereas it correlated positively with the anti-inflammatory cytokines interleukin-10 (IL-10) and IL-1 receptor antagonist, and the bifunctional cytokine tumor necrosis factor α, with respect to PDAC development (P < .05). sMICA also correlated positively with the chemotactic/proangiogenic cytokines vascular endothelial growth factor, soluble CD40 ligand, and IL-8, and the tumor growth-stimulatory cytokines epidermal growth factor and transforming growth factor α, with respect to PDAC development and/or progression. Logistic regression analysis validated the diagnostic usefulness of combination use of sMICA and its related cytokines to predict the presence of PDAC and distant metastasis in PDAC, superior to carbohydrate antigen 19-9.


CONCLUSIONS
sMICA may be involved in tumor-associated angiogenesis and tumor growth either directly or indirectly by affecting corresponding cytokines as well as causing impairment of natural killer cell cytotoxicity in the development and progression of PDAC. A combination of sMICA and its related cytokines exhibited remarkable diagnostic potential in PDAC.
Department of Internal Medicine, Division of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Hye Won
HW
Chung
Sunphil
S
Jang
Jong-Baeck
JB
Lim
D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A