Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study
Abstract Background Early-onset breast cancer (EOBC) affects about one in 300 women aged 40 years or younger and is associated with worse outcomes than later onset breast cancer. This study explored novel serum proteins as surrogate markers of prognosis in patients with EOBC. Methods Serum samples f...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | Breast Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13058-018-0938-6 |
| _version_ | 1818461134245593088 |
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| author | Bashar Zeidan Antigoni Manousopoulou Diana J. Garay-Baquero Cory H. White Samantha E. T. Larkin Kathleen N. Potter Theodoros I. Roumeliotis Evangelia K. Papachristou Ellen Copson Ramsey I. Cutress Stephen A. Beers Diana Eccles Paul A. Townsend Spiros D. Garbis |
| author_facet | Bashar Zeidan Antigoni Manousopoulou Diana J. Garay-Baquero Cory H. White Samantha E. T. Larkin Kathleen N. Potter Theodoros I. Roumeliotis Evangelia K. Papachristou Ellen Copson Ramsey I. Cutress Stephen A. Beers Diana Eccles Paul A. Townsend Spiros D. Garbis |
| author_sort | Bashar Zeidan |
| collection | DOAJ |
| description | Abstract Background Early-onset breast cancer (EOBC) affects about one in 300 women aged 40 years or younger and is associated with worse outcomes than later onset breast cancer. This study explored novel serum proteins as surrogate markers of prognosis in patients with EOBC. Methods Serum samples from EOBC patients (stages 1–3) were analysed using agnostic high-precision quantitative proteomics. Patients received anthracycline-based chemotherapy. The discovery cohort (n = 399) either had more than 5-year disease-free survival (DFS) (good outcome group, n = 203) or DFS of less than 2 years (poor outcome group, n = 196). Expressed proteins were assessed for differential expression between the two groups. Bioinformatics pathway and network analysis in combination with literature research were used to determine clinically relevant proteins. ELISA analysis against an independent sample set from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort (n = 181) was used to validate expression levels of the selected target. Linear and generalized linear modelling was applied to determine the effect of target markers, body mass index (BMI), lymph node involvement (LN), oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 status on patients’ outcome. Results A total of 5346 unique proteins were analysed (peptide FDR p ≤ 0.05). Of these, 812 were differentially expressed in the good vs poor outcome groups and showed significant enrichment for the insulin signalling (p = 0.01) and the glycolysis/gluconeogenesis (p = 0.01) pathways. These proteins further correlated with interaction networks involving glucose and fatty acid metabolism. A consistent nodal protein to these metabolic networks was resistin (upregulated in the good outcome group, p = 0.009). ELISA validation demonstrated resistin to be upregulated in the good outcome group (p = 0.04), irrespective of BMI and ER status. LN involvement was the only covariate with a significant association with resistin measurements (p = 0.004). An ancillary in-silico observation was the induction of the inflammatory response, leucocyte infiltration, lymphocyte migration and recruitment of phagocytes (p < 0.0001, z-score > 2). Survival analysis showed that resistin overexpression was associated with improved DFS. Conclusions Higher circulating resistin correlated with node-negative patients and longer DFS independent of BMI and ER status in women with EOBC. Overexpression of serum resistin in EOBC may be a surrogate indicator of improved prognosis. |
| first_indexed | 2024-12-14T23:41:19Z |
| format | Article |
| id | doaj.art-186df17c7b314cb1a4df42f22cc12b09 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-14T23:41:19Z |
| publishDate | 2018-03-01 |
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| series | Breast Cancer Research |
| spelling | doaj.art-186df17c7b314cb1a4df42f22cc12b092022-12-21T22:43:30ZengBMCBreast Cancer Research1465-542X2018-03-0120111210.1186/s13058-018-0938-6Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics studyBashar Zeidan0Antigoni Manousopoulou1Diana J. Garay-Baquero2Cory H. White3Samantha E. T. Larkin4Kathleen N. Potter5Theodoros I. Roumeliotis6Evangelia K. Papachristou7Ellen Copson8Ramsey I. Cutress9Stephen A. Beers10Diana Eccles11Paul A. Townsend12Spiros D. Garbis13Cancer Sciences Unit, Faculty of Medicine, University of SouthamptonInstitute for Life Sciences, University of SouthamptonInstitute for Life Sciences, University of SouthamptonClinical and Experimental Sciences Unit, Faculty of Medicine, University of SouthamptonCancer Sciences Unit, Faculty of Medicine, University of SouthamptonCancer Sciences Unit, Faculty of Medicine, University of SouthamptonInstitute for Life Sciences, University of SouthamptonInstitute for Life Sciences, University of SouthamptonCancer Sciences Unit, Faculty of Medicine, University of SouthamptonCancer Sciences Unit, Faculty of Medicine, University of SouthamptonCancer Sciences Unit, Faculty of Medicine, University of SouthamptonCancer Sciences Unit, Faculty of Medicine, University of SouthamptonDivision of Cancer Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Science, Manchester Biomedical Research Centre, Health Innovation ManchesterCancer Sciences Unit, Faculty of Medicine, University of SouthamptonAbstract Background Early-onset breast cancer (EOBC) affects about one in 300 women aged 40 years or younger and is associated with worse outcomes than later onset breast cancer. This study explored novel serum proteins as surrogate markers of prognosis in patients with EOBC. Methods Serum samples from EOBC patients (stages 1–3) were analysed using agnostic high-precision quantitative proteomics. Patients received anthracycline-based chemotherapy. The discovery cohort (n = 399) either had more than 5-year disease-free survival (DFS) (good outcome group, n = 203) or DFS of less than 2 years (poor outcome group, n = 196). Expressed proteins were assessed for differential expression between the two groups. Bioinformatics pathway and network analysis in combination with literature research were used to determine clinically relevant proteins. ELISA analysis against an independent sample set from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort (n = 181) was used to validate expression levels of the selected target. Linear and generalized linear modelling was applied to determine the effect of target markers, body mass index (BMI), lymph node involvement (LN), oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 status on patients’ outcome. Results A total of 5346 unique proteins were analysed (peptide FDR p ≤ 0.05). Of these, 812 were differentially expressed in the good vs poor outcome groups and showed significant enrichment for the insulin signalling (p = 0.01) and the glycolysis/gluconeogenesis (p = 0.01) pathways. These proteins further correlated with interaction networks involving glucose and fatty acid metabolism. A consistent nodal protein to these metabolic networks was resistin (upregulated in the good outcome group, p = 0.009). ELISA validation demonstrated resistin to be upregulated in the good outcome group (p = 0.04), irrespective of BMI and ER status. LN involvement was the only covariate with a significant association with resistin measurements (p = 0.004). An ancillary in-silico observation was the induction of the inflammatory response, leucocyte infiltration, lymphocyte migration and recruitment of phagocytes (p < 0.0001, z-score > 2). Survival analysis showed that resistin overexpression was associated with improved DFS. Conclusions Higher circulating resistin correlated with node-negative patients and longer DFS independent of BMI and ER status in women with EOBC. Overexpression of serum resistin in EOBC may be a surrogate indicator of improved prognosis.http://link.springer.com/article/10.1186/s13058-018-0938-6Quantitative serum proteomicsResistinInsulin resistanceGlycolysis/gluconeogenesislymph-node involvementEarly-onset breast cancer |
| spellingShingle | Bashar Zeidan Antigoni Manousopoulou Diana J. Garay-Baquero Cory H. White Samantha E. T. Larkin Kathleen N. Potter Theodoros I. Roumeliotis Evangelia K. Papachristou Ellen Copson Ramsey I. Cutress Stephen A. Beers Diana Eccles Paul A. Townsend Spiros D. Garbis Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study Breast Cancer Research Quantitative serum proteomics Resistin Insulin resistance Glycolysis/gluconeogenesis lymph-node involvement Early-onset breast cancer |
| title | Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study |
| title_full | Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study |
| title_fullStr | Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study |
| title_full_unstemmed | Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study |
| title_short | Increased circulating resistin levels in early-onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival: a multi-center POSH cohort serum proteomics study |
| title_sort | increased circulating resistin levels in early onset breast cancer patients of normal body mass index correlate with lymph node negative involvement and longer disease free survival a multi center posh cohort serum proteomics study |
| topic | Quantitative serum proteomics Resistin Insulin resistance Glycolysis/gluconeogenesis lymph-node involvement Early-onset breast cancer |
| url | http://link.springer.com/article/10.1186/s13058-018-0938-6 |
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