Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2020
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/107940 http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7464257&blobtype=pdf https://www.mdpi.com/2072-6694/12/8/2227 |
| Aporte de: |
| id |
I19-R120-10915-107940 |
|---|---|
| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Medicina rectal cancer immune response gene expression neoadjuvant chemoradiotherapy biomarker |
| spellingShingle |
Medicina rectal cancer immune response gene expression neoadjuvant chemoradiotherapy biomarker Sendoya, Juan M. Iseas, Soledad Coraglio, Mariana Golubicki, Mariano Robbio, Juan Salanova, Ruben Kujaruk, Mirta Mikolaitis, Vanesa Rizzolo, Mariana Ruiz, Gonzalo Cabanne, Ana Gualdrini, Ubaldo Mendez, Guillermo Hirmas, Stella Rotondaro, Cecilia Viglino, Julieta Eleta, Martín Fernandez, Elmer Abba, Martín Carlos Podhajcer, Osvaldo Roca, Enrique Llera, Andrea S. Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer |
| topic_facet |
Medicina rectal cancer immune response gene expression neoadjuvant chemoradiotherapy biomarker |
| description |
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/m<sup>2</sup>/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 <i>RAS</i> and <i>TP53</i> 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 <i>RAS</i> and <i>TP53</i> mutations along with a proficient DNA repair system that may counteract chemoradio-induced DNA damage was associated with poor response. |
| format |
Articulo Articulo |
| author |
Sendoya, Juan M. Iseas, Soledad Coraglio, Mariana Golubicki, Mariano Robbio, Juan Salanova, Ruben Kujaruk, Mirta Mikolaitis, Vanesa Rizzolo, Mariana Ruiz, Gonzalo Cabanne, Ana Gualdrini, Ubaldo Mendez, Guillermo Hirmas, Stella Rotondaro, Cecilia Viglino, Julieta Eleta, Martín Fernandez, Elmer Abba, Martín Carlos Podhajcer, Osvaldo Roca, Enrique Llera, Andrea S. |
| author_facet |
Sendoya, Juan M. Iseas, Soledad Coraglio, Mariana Golubicki, Mariano Robbio, Juan Salanova, Ruben Kujaruk, Mirta Mikolaitis, Vanesa Rizzolo, Mariana Ruiz, Gonzalo Cabanne, Ana Gualdrini, Ubaldo Mendez, Guillermo Hirmas, Stella Rotondaro, Cecilia Viglino, Julieta Eleta, Martín Fernandez, Elmer Abba, Martín Carlos Podhajcer, Osvaldo Roca, Enrique Llera, Andrea S. |
| author_sort |
Sendoya, Juan M. |
| title |
Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_short |
Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_full |
Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_fullStr |
Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_full_unstemmed |
Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer |
| title_sort |
pre-existing tumoral b cell infiltration and impaired genome maintenance correlate with response to chemoradiotherapy in locally advanced rectal cancer |
| publishDate |
2020 |
| url |
http://sedici.unlp.edu.ar/handle/10915/107940 http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7464257&blobtype=pdf https://www.mdpi.com/2072-6694/12/8/2227 |
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