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

Fecha de publicación:

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

Esmo Open  BMJ PUBLISHING GROUP

Tipo:
Article
Páginas:
-
PubMed:
32967918

Citas Recibidas en Web of Science: 28

Métricas

Filiaciones mostrar / ocultar

Keywords

  • consensus molecular subtypes; CDX2 homeoprotein; colon cancer; interleukin-6; plasma circulating-tumor DNA

Financiación

Proyectos y Estudios Clínicos

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CONTRATOS JUAN RODES

Investigador Principal: DESAMPARADOS RODA PEREZ

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JR17/00026 AYUDA JOAN RODÉS DRA. TANIA FLEITAS /2017/322)

Investigador Principal: TANIA CAROLINA FLEITAS KANONNIKOFF

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CA18/00042 (TÉCNICOS BIOINFORMÁTICOS) DRA. SHEILA ZUÑIGA (2018/115)

Investigador Principal: SHEILA MELISA ZÚÑIGA TREJOS

CA18/00042 . INSTITUTO SALUD CARLOS III . 2019

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