Evan N Cohen1,2, Tamer M Fouad1,3,4, Bang-Ning Lee1,2,5, Banu K Arun3, Diane Liu6, Sanda Tin1,2, Angelica M Gutierrez Barrera3, Toshihide Miura7, Iwao Kiyokawa7, Jun Yamashita7, Ricardo H Alvarez1,3,8, Vicente Valero3, Wendy A Woodward1,9, Yu Shen6, Naoto T Ueno1,3, Massimo Cristofanilli1,3,10, James M Reuben11,12. 1. Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1220 Holcombe Blvd, Houston, TX, 77030, USA. 2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. 3. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Unit 3552, Houston, TX, 77030, USA. 4. Department of Medical Oncology, The National Cancer Institute, Cairo University, Kasr El-Aini Road, Cairo, 11796, Egypt. 5. Michael E. DeBakey Veterans Affairs Medical Center, Conroe, TX, USA. 6. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, TX, 77030, USA. 7. Nittobo Medical Co., Ltd., 1, Shiojima Fukuhara, Fukuyama, Koriyama, Fukushima, Japan. 8. Cancer Treatment Centers of America, Newnan, GA, USA. 9. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Unit 76468, Houston, TX, 77030, USA. 10. Feinberg School of Medicine, Northwestern Univeristy, Chicago, IL, USA. 11. Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1220 Holcombe Blvd, Houston, TX, 77030, USA. jreuben@mdanderson.org. 12. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. jreuben@mdanderson.org.
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.
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 cancerpatients (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.
Entities:
Keywords:
Breast cancer; Inflammatory cytokines; Serum; Sialyl Lewisx (SLEX)
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