Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer.

Autores de INCLIVA
Participantes ajenos a INCLIVA
- Calon, Alexandre
- Fontana, Elisa
- Eason, Katherine
- Nyamundanda, Gift
- Sadanandam, Anguraj
Grupos y Plataformas de I+D+i
Abstract
BACKGROUND: Colon cancer (CC) is a heterogeneous disease. Novel prognostic factors beyond pathological staging are required to accurately identify patients at higher risk of relapse. Integrating these new biological factors, such as plasma circulating tumour DNA (ctDNA), CDX2 staining, inflammation-associated cytokines and transcriptomic consensus molecular subtypes (CMS) classification, into a multimodal approach may improve our accuracy in determining risk of recurrence.; METHODS: One hundred and fifty patients consecutively diagnosed with localised CC were prospectively enrolled in our study. ctDNA was tracked to detect minimal residual disease by droplet digital PCR. CDX2 expression was analysed by immunostaining. Plasma levels of cytokines potentially involved in disease progression were measured using ELISAs. A 96 custom gene panel for nCounter assay was used to classify CC into colorectal cancer assigner and CMS.; RESULTS: Most patients were classified into CMS4 (37%) and CMS2 (28%), followed by CMS1 (20%) and CMS3 (15%) groups. CDX2-negative tumours were enriched in CMS1 and CMS4 subtypes. In univariable analysis, prognosis was influenced by primary tumour location, stage, vascular and perineural invasion together with high interleukin-6 plasma levels at baseline, tumours belonging to CMS 1 vs CMS2 +CMS3, ctDNA presence in plasma and CDX2 loss. However, only positive ctDNA in plasma samples (HR 13.64; p=0.002) and lack of CDX2 expression (HR 23.12; p=0.001) were found to be independent prognostic factors for disease-free survival in the multivariable model.; CONCLUSIONS: ctDNA detection after surgery and lack of CDX2 expression identified patients at very high risk of recurrence in localised CC. © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.
© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology
Datos de la publicación
- ISSN/ISSNe:
- 2059-7029, 2059-7029
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 32967918
Esmo Open BMJ PUBLISHING GROUP
Citas Recibidas en Web of Science: 28
Documentos
Filiaciones
Keywords
- consensus molecular subtypes; CDX2 homeoprotein; colon cancer; interleukin-6; plasma circulating-tumor DNA
Financiación
Proyectos y Estudios Clínicos
CONTRATOS RIO HORTEGA
Investigador Principal: NOELIA TARAZONA LLAVERO
CM15/00246 . INSTITUTO SALUD CARLOS III
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Investigador Principal: ANDRÉS CERVANTES RUIPEREZ
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CONTRATOS JUAN RODES
Investigador Principal: DESAMPARADOS RODA PEREZ
2016/197 . INSTITUTO SALUD CARLOS III . 2017
JR17/00026 AYUDA JOAN RODÉS DRA. TANIA FLEITAS /2017/322)
Investigador Principal: TANIA CAROLINA FLEITAS KANONNIKOFF
JR17/00026 . INSTITUTO SALUD CARLOS III . 2018
CA18/00042 (TÉCNICOS BIOINFORMÁTICOS) DRA. SHEILA ZUÑIGA (2018/115)
Investigador Principal: SHEILA MELISA ZÚÑIGA TREJOS
CA18/00042 . INSTITUTO SALUD CARLOS III . 2019
Cita
Tarazona N,Gimeno F,Gambardella V,Huerta M,Rosello S,Zuniga S,Calon A,Carbonell JA,Fontana E,Martinez C,Eason K,Rentero P,Fleitas T,Papaccio F,Moro D,Nyamundanda G,Castillo J,Espi A,Sadanandam A,Roda D,Cervantes A. Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer. ESMO Open. 2020. 5. (5):e000847. IF:6,540. (1).
Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer. Tarazona N, Gimeno F, Gambardella V, Huerta M, Rosello S, Zuniga S, Calon A et al. Esmo Open. 2020 septiembre 01. 5 (5):DOI:10.1136/esmoopen-2020-000847. PMID:32967918.