TY - JOUR
T1 - Elevated serum levels of sialyl Lewis X (sLeX) and inflammatory mediators in patients with breast cancer
AU - Cohen, Evan N.
AU - Fouad, Tamer M.
AU - Lee, Bang Ning
AU - Arun, Banu K.
AU - Liu, Diane
AU - Tin, Sanda
AU - Gutierrez Barrera, Angelica M.
AU - Miura, Toshihide
AU - Kiyokawa, Iwao
AU - Yamashita, Jun
AU - Alvarez, Ricardo H.
AU - Valero, Vicente
AU - Woodward, Wendy A.
AU - Shen, Yu
AU - Ueno, Naoto T.
AU - Cristofanilli, Massimo
AU - Reuben, James M.
N1 - Funding Information:
Funding This work was supported by a Grant from the State of Texas Rare and Aggressive Breast Cancer Research Program, which supports The University of Texas MD Anderson Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, a grant from the National Institutes of Health (R01CA138239), MD Anderson’s Cancer Center Support Grant (P30CA016672), and by research support from Nittobo Medical Co., Japan.
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/8/15
Y1 - 2019/8/15
N2 - Purpose: The carbohydrate sialyl LewisX (sLeX) 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 sLeX and inflammatory cytokines/chemokines in breast cancer sera. Methods: We retrospectively measured sLeX 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 sLeX 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 sLeX using a cut-off of 8 U/mL as previously defined. Results: Median serum sLeX 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 sLeX > 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). sLeX, MCP-1 and IP-10 remained significant in multivariate survival analysis. Conclusion: Elevated serum sLeX was associated with invasive cancer but not DCIS. High serum sLeX 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 sLeX may have prognostic value in breast cancer.
AB - Purpose: The carbohydrate sialyl LewisX (sLeX) 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 sLeX and inflammatory cytokines/chemokines in breast cancer sera. Methods: We retrospectively measured sLeX 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 sLeX 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 sLeX using a cut-off of 8 U/mL as previously defined. Results: Median serum sLeX 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 sLeX > 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). sLeX, MCP-1 and IP-10 remained significant in multivariate survival analysis. Conclusion: Elevated serum sLeX was associated with invasive cancer but not DCIS. High serum sLeX 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 sLeX may have prognostic value in breast cancer.
KW - Breast cancer
KW - Inflammatory cytokines
KW - Serum
KW - Sialyl Lewis (SLE)
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U2 - 10.1007/s10549-019-05258-0
DO - 10.1007/s10549-019-05258-0
M3 - Article
C2 - 31054033
AN - SCOPUS:85065224236
SN - 0167-6806
VL - 176
SP - 545
EP - 556
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -
