Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer
Valentina Gambardella,
Andrés Cervantes,
Elisa Fontana,
Katherine Eason,
Anguraj Sadanandam,
Carolina Martinez-Ciarpaglini,
Marisol Huerta,
Susana Rosello,
Desamparados Roda,
Noelia Tarazona,
Federica Papaccio,
Francisco Gimeno-Valiente,
Sheila Zuniga,
Alexandre Calon,
Juan Antonio Carbonell-Asins,
Pilar Rentero-Garrido,
Tania Fleitas,
David Moro-Valdezate,
Gift Nyamundanda,
Josefa Castillo,
Alejandro Espí
Affiliations
Valentina Gambardella
Department of Medical Oncology, Hospital Clinico Universitario of Valencia, Biomedical Research Institute, INCLIVA, CIBERONC and University of Valencia, Valencia, Spain
Andrés Cervantes
Department of Medical Oncology, Hospital Clinico Universitario of Valencia, Biomedical Research Institute INCLIVA, CIBERONC and University of Valencia, Valencia, Spain
Elisa Fontana
Molecular Pathology, The Institute of Cancer Research, Sutton, UK
Katherine Eason
4 Division of Molecular Pathology, The Institute of Cancer Research, London, UK
Anguraj Sadanandam
4 Division of Molecular Pathology, The Institute of Cancer Research, London, UK
Carolina Martinez-Ciarpaglini
Department of Pathology, Hospital Clinico Universitario of Valencia, Biomedical Research Institute INCLIVA, Valencia, Spain
Marisol Huerta
Department of Medical Oncology, Biomedical Research Institute INCLIVA, CIBERONC, University of Valencia, Valencia, Spain
Susana Rosello
Department of Medical Oncology, Biomedical Research Institute INCLIVA, CIBERONC, University of Valencia, Valencia, Spain
Desamparados Roda
Department of Medical Oncology, Biomedical Research Institute INCLIVA, CIBERONC, University of Valencia, Valencia, Spain
Noelia Tarazona
Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain
Federica Papaccio
Medical Oncology, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
Francisco Gimeno-Valiente
Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain
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.
