Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 176, Issue 3, Pages 545-556Publisher
SPRINGER
DOI: 10.1007/s10549-019-05258-0
Keywords
Sialyl Lewis(x) (SLEX); Inflammatory cytokines; Breast cancer; Serum
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Funding
- State of Texas Rare and Aggressive Breast Cancer Research Program
- National Institutes of Health [R01CA138239]
- MD Anderson's Cancer Center Support Grant [P30CA016672]
- Nittobo Medical Co., Japan
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PurposeThe carbohydrate sialyl Lewis(X) (sLe(X)) mediates cell adhesion, is critical in the normal function of immune cells, and is frequently over-expressed on cancer cells. We assessed the association, differential levels, and prognostic value of sLe(X) and inflammatory cytokines/chemokines in breast cancer sera.MethodsWe retrospectively measured sLe(X) and a panel of cytokines/chemokines in the sera of 26 non-invasive ductal carcinoma in situ (DCIS), 154 invasive non-metastatic breast cancer (non-MBC), 63 metastatic breast cancer (MBC) patients, and 43 healthy controls. Differences in sLe(X) and inflammatory cytokines among and between patient groups and healthy controls were assessed with nonparametric tests and we performed survival analysis for the prognostic potential of sLe(X) using a cut-off of 8 U/mL as previously defined.ResultsMedian serum sLe(X) was significantly higher than controls for invasive breast cancer patients (MBC and non-MBC) but not DCIS. In univariate analysis, we confirmed patients with serum sLe(X)>8 U/mL have a significantly shorter progression-free survival (PFS) (P=0.0074) and overall survival (OS (P=0.0003). Similarly, patients with high serum MCP-1 and IP-10 had shorter OS (P=0.001 and P<0.001, respectively) and PFS (P=0.010 and P<0.001, respectively). sLe(X), MCP-1 and IP-10 remained significant in multivariate survival analysis.ConclusionElevated serum sLe(X) was associated with invasive cancer but not DCIS. High serum sLe(X) levels were associated with inflammatory mediators and may play a role in facilitating local invasion of breast tumor. Furthermore, serum MCP-1, IP-10 and sLe(X) may have prognostic value in breast cancer.
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