Whole-transcriptome analysis links trastuzumab sensitivity of breast tumors to both HER2 dependence and immune cell infiltration
| Autor: | Silvana Canevari, Andrea Balsari, Sylvie Ménard, Serena Di Cosimo, Marta Giussani, Aleix Prat, Marialuisa L. Carcangiu, Manuela Campiglio, Daniele Generali, Biagio Paolini, Elda Tagliabue, Loris De Cecco, Alberto Bottini, Tiziana Triulzi, Marco Sandri |
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| Přispěvatelé: | Universitat de Barcelona, Triulzi, Tiziana, Cecco, Loris De, Sandri, Marco, Prat, Aleix, Giussani, Marta, Paolini, Biagio, Carcangiu, Marialuisa L., Canevari, Silvana, Bottini, Alberto, Balsari, Andrea, Menard, Sylvie, Generali, Daniele, Campiglio, Manuela, Cosimo, Serena Di, Tagliabue, Elda |
| Rok vydání: | 2015 |
| Předmět: |
lymphocytes
Oncology Trastuzumab benefit Receptor ErbB-2 medicine.medical_treatment Kaplan-Meier Estimate CD8-Positive T-Lymphocytes Antineoplastic Agent Cohort Studies Transcriptome ErbB-2 Breast cancer Models Risk Factors Trastuzumab Gene Regulatory Networks Lymphocytes skin and connective tissue diseases Adjuvant Neoadjuvant therapy Oligonucleotide Array Sequence Analysis Gene Regulatory Network Prognosis Immunohistochemistry Neoadjuvant Therapy trastuzumab benefit Gene Expression Regulation Neoplastic Local Chemotherapy Adjuvant Lymphocyte Female Breast Neoplasm Human Receptor Research Paper medicine.drug medicine.medical_specialty Prognosi Antineoplastic Agents Breast Neoplasms Therapeutics Limfòcits Càncer de mama breast cancer Immune system Genetic Internal medicine gene expression profiling medicine Chemotherapy Humans Gene expression profiling Estrogen Receptor alpha Models Genetic Neoplasm Recurrence Local Gene Expression Profiling neoplasms Neoplastic Oligonucleotide Array Sequence Analysi business.industry Risk Factor CD8-Positive T-Lymphocyte Terapèutica medicine.disease Expressió gènica Neoplasm Recurrence Gene Expression Regulation Immunology Monoclonal antibodies Gene expression Cohort Studie business Anticossos monoclonals |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | While results thus far demonstrate the clinical benefit of trastuzumab, some patients do not respond to this therapy. To identify a molecular predictor of trastuzumab benefit, we conducted whole-transcriptome analysis of primary HER2+ breast carcinomas obtained from patients treated with trastuzumab-containing therapies and correlated the molecular portrait with treatment benefit. The estimated association between gene expression and relapse-free survival allowed development of a trastuzumab risk model (TRAR), with ERBB2 and ESR1 expression as core elements, able to identify patients with high and low risk of relapse. Application of the TRAR model to 24 HER2+ core biopsies from patients treated with neo-adjuvant trastuzumab indicated that it is predictive of trastuzumab response. Examination of TRAR in available whole-transcriptome datasets indicated that this model stratifies patients according to response to trastuzumab-based neo-adjuvant treatment but not to chemotherapy alone. Pathway analysis revealed that TRAR-low tumors expressed genes of the immune response, with higher numbers of CD8-positive cells detected immunohistochemically compared to TRAR-high tumors. The TRAR model identifies tumors that benefit from trastuzumab-based treatment as those most enriched in CD8-positive immune infiltrating cells and with high ERBB2 and low ESR1 mRNA levels, indicating the requirement for both features in achieving trastuzumab response. |
| Databáze: | OpenAIRE |
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