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Poster Discussion session - Translational research 1

1989 - Identification of biological axes associated with stage II/III CRC recurrence risk and outcome after adjuvant therapy revealed a T-effector-independent prognostic role for granzyme B.


20 Oct 2018


Poster Discussion session - Translational research 1


Translational Research

Tumour Site

Colon and Rectal Cancer


Pierre Laurent-Puig


Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269


P. Laurent-Puig1, L. Marisa2, M. Ayadi2, Y. Blum2, R. Balogoun1, C. Pilati1, K. Le Malicot3, C. Lepage4, J.F. Emile5, R. Salazar6, D. Aust7, A. Duval8, J. Selves9, D. Guenot10, G. Milano11, J. Seitz12, J. Taieb13, V. Boige14, A. de Reyniès15

Author affiliations

  • 1 Umr-s1147, Paris Descartes University, 75006 - Paris/FR
  • 2 Programme ‘cartes D’identité Des Tumeurs’, Ligue Nationale contre le cancer, 75013 - Paris/FR
  • 3 Epicad Inserm Lnc-umr 1231, Burgandy university, Dijon/FR
  • 4 Department Of Hepato Gastroenterology And Digestive Oncology, University of Burgundy and Franche-Comté, 21079 - Dijon/FR
  • 5 Anatomie Cytologie Pathologiques, Hopital Ambroise Pare, 92100 - Boulogne-Billancourt/FR
  • 6 Oncology, Institut Català d'Oncologia Hospital Duran i Reynals, 08907 - Barcelona/ES
  • 7 Pathology, Universitätsklinikum Dresden, 01307 - Dresden/DE
  • 8 Inserm Umr1102, Pierre et Marie Curie University, Paris/FR
  • 9 Département De Pathologie, Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse/FR
  • 10 Ea3430, Strasbourg university, Strasbourg/FR
  • 11 Biology, Centre antoine Lacassagne, Nice/FR
  • 12 Oncology, CHU La Timone Enfants, 13385 - Marseille/FR
  • 13 Department Of Gastroenterology And Digestive Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 14 Medicine, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 15 Biostatistique, La Ligue Contre Le Cancer, 75014 - Paris/FR

Abstract 1989


The consensus molecular subtypes (CMS) of colon cancer only accounts for inter-tumor heterogeneity so far. To overcome this limitation and describe intratumor heterogeneity, we split colon tumor transcriptomes as weighted linear combinations of the four CMS. This leads to identify pure samples, corresponding to a unique CMS, and mixed samples, corresponding to several CMS. Using the PETACC8 cohort, we evaluate the prognostic impact of this new weighted CMS classification.


Paired Nanostring and Affymetrix data were available for the CIT training series (n = 198). NanoString expression data (172 genes) were available for 1779 samples from the PETACC8 trial validation cohort. A random forest classifier (rfc) of the CMS was trained on the Nanostring CIT data and then applied to PETACC8 samples. Using linear regressions, we identified for each sample the weighted linear combination of CMS centroids with minimal distance to its transcriptome profile.


Applying rfc to PETACC8 confirmed clinical and molecular data of the CMS classification previously published. Applying the weighted classifier to PETACC8 yielded 42.6% of pure tumors, displaying a unique CMS signature, and 57.4% of mixed tumors, displaying at least 2 CMS signatures (each weighting more than 20%). Mixed tumors were synthetized by their top 2 CMS components (major/minor). Therefore, we defined 16 subgroups with prevalence ranging from 2.1% to 18.3%. MMR deficiency and BRAF mutations were found enriched in pure CMS1, CMS1/CMS3 and CMS3/CMS1 mixed tumors. The pure CMS3 was the only subtype enriched for RAS mutations. For DFS univariate Cox analysis of this 16 subtype classification revealed a significant worse prognostic impact of CMS4 signature either pure or combined to any other CMS signature. The worst prognostic was observed in CMS3/CMS4 subtype (HR = 2.43 CI[1.6-3.7], followed by CMS1/CMS4 (HR = 2.36 CI[1.5-3.6] CMS4/CMS1 (HR = 2.3 CI[1.6-3.5]), CMS1/CMS3 (HR = 2 CI[1.3-3.1]) and CMS4/CMS3 (HR = 1.9 CI[1.2-3]) . These results were confirmed after adjusting for significant clinical variables.


Taking into account the intra tumor heterogeneity brings additional information to colon cancer stage III prognostication.

Clinical trial identification

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive.


Merck KGA.

Editorial Acknowledgement


All authors have declared no conflicts of interest.

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