72P Correlation of serum cytokine patterns and clinicopathological factors in breast carcinoma patients

Abstract

Recent evidence support that the immune system has both positive and negative effects on tumorigenesis. Systemic inflammation has been linked to aggressive tumor growth, metastasis, and drug resistance in breast cancer (BC) patients. Therefore, serum cytokines (SC) may represent an exciting biomarker in the monitoring of BC pathogenesis. Pretreatment serum from 204 BC patients (23% Luminal A, 23.6% Luminal B/HER2-, 22.5% Luminal B/HER2+, 10.3% HER2-enriched, and 20.6% Triple-Negative/Basal-like -TNBL-) and 50 healthy donors was collected. Measurement of 62 SC was performed using LEGENDplex immunoassay. Fluorescence intensity was quantified by flow cytometry. The results were correlated with age, tumor size and grade, vascular invasion, necrosis, phenotype, tumor-infiltrating lymphocytes, lymph node status, and Ki67. Statistical analysis was done by Student’s t-test and Mann–Whitney U test. BC patients showed higher levels of SCF, MIP3α, EPO and 4-1BB but lower levels of IL-2RA, IL-8, IL-12p40, IL-18, IL-23, IL-27, PDGF-AA, Galectin 9, PDGF-BB, B7.2, MIP1β and PD1, compared to the healthy group. Furthermore, IL-23, IL-27, and EPO correlated with younger age (p≤0.041), in contrast to Galectin 9, MCP1, IL-2RA, and MIP1β (p≤0.003). IL-12p40 and IFNγ were elevated in cases with grade I tumors (p≤0.05) and, in addition to IL-11 and IL-27 in low Ki67 tumors (p≤0.030). Moreover, IL-12p40 and IL-23 were associated with positive lymph nodes (p≤0.031). In Luminal tumors, we detected high IL-12p40, IL-15, IL-23, IL-27, and IFNγ (p≤0.048). However, only PDGF-BB was seen in non-Luminal tumor patients (p=0.040). IL-12p40, IL-18, IL-23, IL-27, SCF, and EPO were mainly higher in Luminal A, while PDGF-AA in Luminal B/HER2-. Likewise, MIP1β, MIP3α, and EPO were elevated in Luminal B/HER2+ serum, whereas Galectin9, PDGF-BB, IL-2RA, B7.2, SCF, 4-1BB, and PD1 were found in TNBL, with no specific profile for HER2-enriched. Our results showed specific serum profiles of SC among BC phenotypes. Moreover, IL-12p40 and IL-23 were correlated with lymph node involvement in Luminal tumors, especially in Luminal A.