2024-03-28T16:25:59Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2096662021-12-28T15:53:12Zcom_10261_112com_10261_1col_10261_365
A Transcriptomic Immunologic Signature Predicts Favorable Outcome in Neoadjuvant Chemotherapy Treated Triple Negative Breast Tumors
Pérez-Peña, Javier
Tibor Fekete, Janos
Páez, Raquel
Baliu-Piqué, Mariona
García-Saenz, José Ángel
García-Barberán, Vanesa
Manzano, Aranzazu
Pérez-Segura, Pedro
Esparís-Ogando, Azucena
Pandiella, Atanasio
Győrffy, Balázs
Ocaña, Alberto
Instituto de Salud Carlos III
Acepain Albacete
Diputación de Albacete
Fundación CRIS contra el Cáncer
Ministerio de Economía y Competitividad (España)
Asociación Española Contra el Cáncer
European Commission
Immunotherapy
Triple negative breast cancer
Chemotherapy treated patients
Transcriptomic signature
Outcome
© 2019 Pérez-Pena, Tibor Fekete, Páez, Baliu-Piqué, García-Saenz, García-Barberán, Manzano, Pérez-Segura, Esparis-Ogando, Pandiella, Gyorffy and Ocaña.
Limited therapeutic options exist for the treatment of patients with triple negative breast cancer (TNBC). Neoadjuvant chemotherapy is currently the standard of care treatment in the early stages of the disease, although reliable biomarkers of response have been scarcely described. In our study we explored whether immunologic signatures associated with inflamed tumors or hot tumors could predict the outcome to neoadjuvant chemotherapy. Publicly available transcriptomic data of more than 2,000 patients were evaluated. ROC plots were generated to assess the response to therapy. Cox proportional hazards regression was computed. Kaplan-Meier plots were drawn to visualize the survival differences. Higher expression of IDO1, CXCL9, CXCL10, HLA-DRA, HLA-E, STAT1, and GZMB were associated with a higher proportion without relapse in the first 5 y after chemotherapy in TNBC. The expression of these genes was associated with a high presence of CD8 T cells in responder patients using the EPIC bioinformatic tool. The strongest effect was observed for STAT1 (p = 1.8e-05 and AUC 0.69, p = 2.7e-06). The best gene-set signature to predict favorable RFS was the combination of IDO1, LAG3, STAT1, and GZMB (HR = 0.28, CI = 0.17–0.46, p = 9.8 E-08, FDR = 1%). However, no influence on pathological complete response (pCR) was observed. Similarly, no benefit was identified in any other tumor subtype: HER2 or estrogen receptor positive. In conclusion, we describe a set of immunologic genes that predict the outcome to neoadjuvant chemotherapy in TNBC, but not pCR, suggesting that this non-time to event endpoint is not a good surrogate marker to detect the long term outcome for immune activated tumors.
2020-04-29T12:53:32Z
2020-04-29T12:53:32Z
2019-12-18
2020-04-29T12:53:33Z
artículo
Frontiers in Immunology 10: 2802 (2019)
http://hdl.handle.net/10261/209666
10.3389/fimmu.2019.02802
1664-3224
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100003329
31921107
Publisher's version
http://dx.doi.org/10.3389/fimmu.2019.02802
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2015-71371-R
http://creativecommons.org/licenses/by/4.0/
openAccess
Frontiers Media