A combination of extracellular matrix‐ and interferon‐associated signatures identifies high‐grade breast cancers with poor prognosis
Autor: | Mara Lecchi, Paolo Verderio, Vera Cappelletti, Francesca De Santis, Biagio Paolini, Melissa Monica, Sabina Sangaletti, Serenella Maria Pupa, Marilena Valeria Iorio, Giulia Bianchi, Massimiliano Gennaro, Giovanni Fucà, Filippo De Braud, Elda Tagliabue, Massimo Di Nicola |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: | |
Zdroj: | Molecular Oncology, Vol 15, Iss 5, Pp 1345-1357 (2021) |
Druh dokumentu: | article |
ISSN: | 1878-0261 1574-7891 |
DOI: | 10.1002/1878-0261.12912 |
Popis: | Breast cancer (BC) is a heterogeneous disease in which the tumor microenvironment (TME) seems to impact the clinical outcome. Here, we investigated whether a combination of gene expression signatures relating to both the structural and immune TME aspects can help predict prognosis in women with high‐grade BC (HGBC). Thus, we focused on a combined molecular biomarker variable that involved extracellular matrix (ECM)‐associated gene expression (ECM3 signature) and interferon (IFN)‐associated metagene (IFN metagene) expression. In 97 chemo‐naive HGBCs from the METABRIC dataset, the dichotomous ECM3/IFN (dECIF) variable identified a group of high‐risk patients (ECM3+/IFN− vs other; hazard ratio = 3.2, 95% confidence interval: 1.5–6.7). Notably, ECM3+/IFN− tumors showed low tumor‐infiltrating lymphocytes, high levels of CD33‐positive cells, absence of PD‐1 expression, or low expression of PD‐L1, as suggested by immune profiles and immune‐histochemical analysis on an independent cohort of 131 HGBCs. To make our results transferable to clinical use, we refined the dECIF biomarker using reduced ECM3 and IFN signatures; notably, the prognostic value of this reduced dECIF was comparable to that of the original dECIF. After validation in a new BC cohort, reduced dECIF was translated into a robust qPCR classifier for real‐world clinical use. |
Databáze: | Directory of Open Access Journals |
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