Elevated serum levels of sialyl Lewis X (sLeX) and inflammatory mediators in patients with breast cancer

Evan N. Cohen; Tamer M. Fouad; Bang Ning Lee; Banu K. Arun; Diane Liu; Sanda Tin; Angelica M. Gutierrez Barrera; Toshihide Miura; Iwao Kiyokawa; Jun Yamashita; Ricardo H. Alvarez; Vicente Valero; Wendy A. Woodward; Yu Shen; Naoto T. Ueno; Massimo Cristofanilli; James M. Reuben

doi:10.1007/s10549-019-05258-0

Elevated serum levels of sialyl Lewis X (sLe^X) and inflammatory mediators in patients with breast cancer

Evan N. Cohen, Tamer M. Fouad, Bang Ning Lee, Banu K. Arun, Diane Liu, Sanda Tin, Angelica M. Gutierrez Barrera, Toshihide Miura, Iwao Kiyokawa, Jun Yamashita, Ricardo H. Alvarez, Vicente Valero, Wendy A. Woodward, Yu Shen, Naoto T. Ueno, Massimo Cristofanilli, James M. Reuben^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Purpose: The 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. Methods: We 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. Results: Median 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. Conclusion: Elevated 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.

Original language	English (US)
Pages (from-to)	545-556
Number of pages	12
Journal	Breast Cancer Research and Treatment
Volume	176
Issue number	3
DOIs	https://doi.org/10.1007/s10549-019-05258-0
State	Published - Aug 15 2019

Funding

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.

Keywords

Breast cancer
Inflammatory cytokines
Serum
Sialyl Lewis (SLE)

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s10549-019-05258-0

Cite this

Cohen, E. N., Fouad, T. M., Lee, B. N., Arun, B. K., Liu, D., Tin, S., Gutierrez Barrera, A. M., Miura, T., Kiyokawa, I., Yamashita, J., Alvarez, R. H., Valero, V., Woodward, W. A., Shen, Y., Ueno, N. T., Cristofanilli, M., & Reuben, J. M. (2019). Elevated serum levels of sialyl Lewis X (sLe^X) and inflammatory mediators in patients with breast cancer. Breast Cancer Research and Treatment, 176(3), 545-556. https://doi.org/10.1007/s10549-019-05258-0

@article{d00ee513dcf346988aa99de35ad4832f,

title = "Elevated serum levels of sialyl Lewis X (sLeX) and inflammatory mediators in patients with breast cancer",

abstract = "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.",

keywords = "Breast cancer, Inflammatory cytokines, Serum, Sialyl Lewis (SLE)",

author = "Cohen, {Evan N.} and Fouad, {Tamer M.} and Lee, {Bang Ning} and Arun, {Banu K.} and Diane Liu and Sanda Tin and {Gutierrez Barrera}, {Angelica M.} and Toshihide Miura and Iwao Kiyokawa and Jun Yamashita and Alvarez, {Ricardo H.} and Vicente Valero and Woodward, {Wendy A.} and Yu Shen and Ueno, {Naoto T.} and Massimo Cristofanilli and Reuben, {James M.}",

note = "Publisher Copyright: {\textcopyright} 2019, Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2019",

month = aug,

day = "15",

doi = "10.1007/s10549-019-05258-0",

language = "English (US)",

volume = "176",

pages = "545--556",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer",

number = "3",

}

Cohen, EN, Fouad, TM, Lee, BN, Arun, BK, Liu, D, Tin, S, Gutierrez Barrera, AM, Miura, T, Kiyokawa, I, Yamashita, J, Alvarez, RH, Valero, V, Woodward, WA, Shen, Y, Ueno, NT, Cristofanilli, M & Reuben, JM 2019, 'Elevated serum levels of sialyl Lewis X (sLe^X) and inflammatory mediators in patients with breast cancer', Breast Cancer Research and Treatment, vol. 176, no. 3, pp. 545-556. https://doi.org/10.1007/s10549-019-05258-0

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.

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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