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Published in: Cancer Immunology, Immunotherapy 1/2019

01-01-2019 | Original Article

Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics

Authors: Sotirios P. Fortis, Christoforos K. Vaxevanis, Louisa G. Mahaira, Michael Sofopoulos, Nectaria N. Sotiriadou, Amalia Dinou, Niki Arnogiannaki, Catherine Stavropoulos-Giokas, Dimitris Thanos, Constantin N. Baxevanis, Sonia A. Perez

Published in: Cancer Immunology, Immunotherapy | Issue 1/2019

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Abstract

Breast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23α, miR-146α, miR-155 and miR-181α), in operable BCa patients, with non-metastatic, invasive ductal carcinoma, not receiving neoadjuvant chemotherapy. These miRNAs, known to be involved in both tumor cell progression and immune pathways regulation, were analyzed in relation to circulating cytokines, tumor immune-cell infiltration and established prognostic clinicopathological characteristics. We have identified three different clusters, with overall low (C1), moderate (C2) or high (C3) expression levels of these six circulating miRNAs, which define three distinct groups of non-metastatic BCa patients characterized by different clinicopathological and immune-related characteristics, with possibly different clinical outcomes. Our data provide the proof-of-principle to support the notion that, up- or down-regulation of the same circulating miRNA may reflect different prognosis in BCa. Nonetheless, the prognostic and/or predictive potential of these three “signatures” needs to be further evaluated in larger cohorts of BCa patients with an, at least, 5-year clinical follow-up.
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Literature
4.
go back to reference Ravelli A, Reuben JM, Lanza F, Anfossi S, Cappelletti MR, Zanotti L, Gobbi A, Senti C, Brambilla P, Milani M, Spada D, Pedrazzoli P, Martino M, Bottini A, Generali D,, Marrow Transplantation S (2015) Solid tumor working party of European B. Breast cancer circulating biomarkers: advantages, drawbacks, and new insights. Tumour Biol J Int Soc Oncodev Biol Med 36(9):6653–6665. https://doi.org/10.1007/s13277-015-3944-7 CrossRef Ravelli A, Reuben JM, Lanza F, Anfossi S, Cappelletti MR, Zanotti L, Gobbi A, Senti C, Brambilla P, Milani M, Spada D, Pedrazzoli P, Martino M, Bottini A, Generali D,, Marrow Transplantation S (2015) Solid tumor working party of European B. Breast cancer circulating biomarkers: advantages, drawbacks, and new insights. Tumour Biol J Int Soc Oncodev Biol Med 36(9):6653–6665. https://​doi.​org/​10.​1007/​s13277-015-3944-7 CrossRef
21.
go back to reference Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell research 18(10):997–1006. https://doi.org/10.1038/cr.2008.282 CrossRefPubMed Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell research 18(10):997–1006. https://​doi.​org/​10.​1038/​cr.​2008.​282 CrossRefPubMed
25.
go back to reference Janssen N, Fortis SP, Speigl L, Haritos C, Sotiriadou NN, Sofopoulos M, Arnogiannaki N, Stavropoulos-Giokas C, Dinou A, Perez S, Pawelec G, Baxevanis CN, Shipp C (2017) Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients. Breast Cancer Res Treat 161(1):51–62. https://doi.org/10.1007/s10549-016-4037-z CrossRefPubMed Janssen N, Fortis SP, Speigl L, Haritos C, Sotiriadou NN, Sofopoulos M, Arnogiannaki N, Stavropoulos-Giokas C, Dinou A, Perez S, Pawelec G, Baxevanis CN, Shipp C (2017) Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients. Breast Cancer Res Treat 161(1):51–62. https://​doi.​org/​10.​1007/​s10549-016-4037-z CrossRefPubMed
27.
go back to reference Anastasopoulou EA, Voutsas IF, Keramitsoglou T, Gouttefangeas C, Kalbacher H, Thanos A, Papamichail M, Perez SA, Baxevanis CN (2015) A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit. Cancer Immunol Immunother 64(9):1123–1136. https://doi.org/10.1007/s00262-015-1717-1 CrossRefPubMed Anastasopoulou EA, Voutsas IF, Keramitsoglou T, Gouttefangeas C, Kalbacher H, Thanos A, Papamichail M, Perez SA, Baxevanis CN (2015) A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit. Cancer Immunol Immunother 64(9):1123–1136. https://​doi.​org/​10.​1007/​s00262-015-1717-1 CrossRefPubMed
28.
go back to reference Stokidis S, Dinou A, Fortis SP, Vaxevanis CK, Konstantellou M, Stavropoulos-Giokas C, Perez SA, Baxevanis CN (2017) The impact of HLA-A*02 and HLA-A*24 allele expression in prostate cancer prognosis In: 3rd Symposium on Advances in Cancer Immunology and Immunotherapy, Athens, Greece, November 2–4. https://doi.org/10.13140/RG.2.2.34617.47202 Stokidis S, Dinou A, Fortis SP, Vaxevanis CK, Konstantellou M, Stavropoulos-Giokas C, Perez SA, Baxevanis CN (2017) The impact of HLA-A*02 and HLA-A*24 allele expression in prostate cancer prognosis In: 3rd Symposium on Advances in Cancer Immunology and Immunotherapy, Athens, Greece, November 2–4. https://​doi.​org/​10.​13140/​RG.​2.​2.​34617.​47202
29.
go back to reference Vaxevanis C, Anastasopoulou E, Tzonis P, Ardavanis A, Baxevanis CN, Peoples GE, Perez SA (2017) An IFN-γ response-based algorithm with predictive potential in AE37-vaccinated breast cancer patients In: 3rd Symposium on Advances in Cancer Immunology and Immunotherapy, Athens, Greece, November 2–4 2017. https://doi.org/10.13140/RG.2.2.24551.14248 Vaxevanis C, Anastasopoulou E, Tzonis P, Ardavanis A, Baxevanis CN, Peoples GE, Perez SA (2017) An IFN-γ response-based algorithm with predictive potential in AE37-vaccinated breast cancer patients In: 3rd Symposium on Advances in Cancer Immunology and Immunotherapy, Athens, Greece, November 2–4 2017. https://​doi.​org/​10.​13140/​RG.​2.​2.​24551.​14248
33.
go back to reference Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N (2014) Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 32(33):3744–3752. https://doi.org/10.1200/JCO.2014.55.5730 CrossRefPubMedPubMedCentral Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N (2014) Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 32(33):3744–3752. https://​doi.​org/​10.​1200/​JCO.​2014.​55.​5730 CrossRefPubMedPubMedCentral
Metadata
Title
Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics
Authors
Sotirios P. Fortis
Christoforos K. Vaxevanis
Louisa G. Mahaira
Michael Sofopoulos
Nectaria N. Sotiriadou
Amalia Dinou
Niki Arnogiannaki
Catherine Stavropoulos-Giokas
Dimitris Thanos
Constantin N. Baxevanis
Sonia A. Perez
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 1/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-018-2252-7

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