Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer
| Autor: | Mariano Golubicki, Gonzalo Ruiz, Elmer Andrés Fernández, Martin Eleta, Soledad Iseas, Andrea S. Llera, Stella Hirmas, Mirta Kujaruk, Julieta Viglino, Vanesa Mikolaitis, Juan M. Sendoya, Ubaldo Gualdrini, Juan Robbio, Enrique Roca, Martín Carlos Abba, Osvaldo L. Podhajcer, Mariana Rizzolo, Ruben Salanova, Ana Cabanne, Cecilia Rotondaro, Mariana Coraglio, Guillermo Mendez |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Medicina Colorectal cancer DNA repair lcsh:RC254-282 Article immune response Capecitabine 03 medical and health sciences 0302 clinical medicine neoadjuvant chemoradiotherapy Internal medicine medicine rectal cancer B cell CD20 biology business.industry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein gene expression Biomarker (medicine) Immunohistochemistry biomarker business Chemoradiotherapy medicine.drug |
| Zdroj: | Cancers Volume 12 Issue 8 Cancers, Vol 12, Iss 2227, p 2227 (2020) SEDICI (UNLP) Universidad Nacional de La Plata instacron:UNLP |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12082227 |
| Popis: | Locally advanced rectal cancer (LARC) remains a medical challenge. Reliable biomarkers to predict which patients will significantly respond to neoadjuvant chemoradiotherapy (nCRT) have not been identified. We evaluated baseline genomic and transcriptomic features to detect differences that may help predict response to nCRT. Eligible LARC patients received nCRT (3D-LCRT 50.4 Gy plus capecitabine 825 mg/m2/bid), preceded by three cycles of CAPOX in high systemic-relapse risk tumors, and subsequent surgery. Frozen tumor biopsies at diagnosis were sequenced using a colorectal cancer panel. Transcriptomic data was used for pathway and cell deconvolution inferential algorithms, coupled with immunohistochemical validation. Clinical and molecular data were analyzed according to nCRT outcome. Pathways related to DNA repair and proliferation (p < 0.005), and co-occurrence of RAS and TP53 mutations (p = 0.001) were associated with poor response. Enrichment of expression signatures related to enhanced immune response, particularly B cells and interferon signaling (p < 0.005), was detected in good responders. Immunohistochemical analysis of CD20⁺ cells validated the association of good response with B cell infiltration (p = 0.047). Findings indicate that the presence of B cells is associated with successful tumor regression following nCRT in LARC. The prevalence of simultaneous RAS and TP53 mutations along with a proficient DNA repair system that may counteract chemoradio-induced DNA damage was associated with poor response. Facultad de Ciencias Médicas Centro de Investigaciones Inmunológicas Básicas y Aplicadas |
| Databáze: | OpenAIRE |
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