Identification of serum cytokine clusters associated with outcomes in ovarian clear cell carcinoma

Abstract

Serum cytokine and chemokine networks may reflect the complex systemic immunological interactions in cancer patients. Studying groups of cytokines and their networks may help to understand their clinical biology. A total of 178 cases of ovarian cancer were analyzed in this study, including 73 high-grade serous (HGSC), 66 clear cell (CCC) and 39 endometrioid carcinomas. Suspension cytokine arrays were performed with the patients’ sera taken before the primary surgery. Associations between each cytokine and clinicopathological factors were analyzed in all patients using multivariate linear regression models, and cluster analyses were performed for each histotype. In the multivariate analyses, twelve of 27 cytokines were correlated with histotypes. Cluster analyses in each histotype revealed 2 cytokine signatures S1 and S2 in HGSC, and similarly C1 and C2 in CCC. Twenty-two of 27 cytokines were commonly clustered in HGSC and CCC. Signature S1 and C1 included IL-2,6,8,15, chemokines and angiogenic factors, whereas signature S2 and C2 included IL-4,5,9,10,13, TNF-α and G-CSF. Four subgroups based on a high or low level for each signature were identified, and this cluster-based classification demonstrated significantly different progression-free and overall survivals for CCC patients (P = 0.00097 and P = 0.017).

Integration of local and systemic immunity in ovarian cancer: Implications for immunotherapy

“…Two OC histotypes, i.e., HGSOC and clear cell carcinoma (CCC) shared similar cytokinome signatures involved in the “hemotaxis and angiogenesis” and “Th2-type immunity”. These results indicate that HGSOC and CCC may share a systemic immunological profile ( 149 ).…”

Dysregulation of Peripheral Blood Mononuclear Cells and Immune-Related Proteins during the Early Post-Operative Immune Response in Ovarian Cancer Patients

“…Some of these findings concur with the findings of other investigators [ 19 , 20 , 53 ], although the results from different studies vary. This may be explained by the fact that many factors influence cytokine concentrations, including the stage and histology of OC [ 54 ].…”