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. 2025 May 20;43(15):1765-1776.
doi: 10.1200/JCO.23.02262. Epub 2025 Jan 31.

Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials

Claire Gallois  1   2 , Marine Sroussi  1   3 , Thierry André  4 , Sophie Mouillet-Richard  1 , Natacha Agueeff  1 , Claire Mulot  1 , Dewi Vernerey  5   6 , Christophe Louvet  7 , Jean-Baptiste Bachet  8 , Louis-Marie Dourthe  9 , Thibault Mazard  10 , Marine Jary  11 , Clélia Coutzac  12 , Cédric Lecaille  13 , Josep Tabernero  14 , Jean-Luc Van Laethem  15 , Côme Lepage  16 , Jean-François Emile  17 , Aurélien de Reyniès  1   18 , Julien Taieb  1   2 , Pierre Laurent-Puig  1
Affiliations

Prognostic Models From Transcriptomic Signatures of the Tumor Microenvironment and Cell Cycle in Stage III Colon Cancer From PETACC-8 and IDEA-France Trials

Claire Gallois et al. J Clin Oncol. .

Abstract

Purpose: The objective of this work was to establish prognostic models in stage III colon cancer (CC) on the basis of transcriptomic signatures of the tumor microenvironment (TME) and cell cycle from the PETACC-8 (training set) and IDEA-France (validation set) trials.

Patients and methods: 3'RNA sequencing was performed in 1,733 patients from the PETACC-8 trial and 1,248 patients from the IDEA-France trial. Four transcriptomic signatures were analyzed: T-cell and macrophage M2 signatures, the expression of CXCL13, and a score on the basis of the Oncotype DX CC Recurrence Score using the same formula from the stromal score and the cell cycle score. The Immune Proliferative Stromal (IPS) score was defined as the number of dichotomized signatures that fall under the category of a dismal prognosis (from 0 to 4). Time to recurrence (TTR) was defined as the time from the date of random assignment to local and/or metastatic relapse and/or death because of CC, whichever occurs first.

Results: High Oncotype-like and M2 scores and low CXCL13 expression and T-cell score were associated with a shorter TTR. A multivariable model including these signatures and all known prognostic factors applied to the IDEA-France cohort by obtaining a value of this model for each patient showed TTR significantly different depending on the quartile of this value and a 3-year rate of patients without recurrence ranging from 56% for the lowest quartile to 89% for the highest quartile (P < .0001). The IPS score was significantly associated with TTR in multivariable analysis.

Conclusion: Using transcriptomic data of patients with stage III CC from two large-scale adjuvant trials, a prognostic model on the basis of signatures of the TME and the cell cycle provides important information in addition to known prognostic factors for patient stratification on risk of recurrence.

Trial registration: ClinicalTrials.gov NCT00958737.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Claire Gallois

Consulting or Advisory Role: Servier, Pierre Fabre, MSD, Merck

Travel, Accommodations, Expenses: Pierre Fabre, Servier

Thierry André

Honoraria: Bristol Myers Squibb, Servier, Merck, Merck Serono, Sanofi, Seagen

Consulting or Advisory Role: Bristol Myers Squibb, MSD Oncology, Servier, GlaxoSmithKline, Seagen, Nordic Bioscience, Aptitude Health, Gilead Sciences, Pfizer, Takeda, AbbVie, Nimbus Therapeutics

Travel, Accommodations, Expenses: MSD Oncology, Bristol Myers Squibb, Takeda

Other Relationship: Inspirna

Uncompensated Relationships: ARCAD Foundation, Adjuvant Colon Cancer End Points (ACCENT) Collaborative Group

Dewi Vernerey

Consulting or Advisory Role: OSE Immunotherapeutics, Janssen-Cilag, HalioDx, Pfizer, CellProthera, Gercor, Incyte, Fondazione Smith Kline, Invectys, AC BioScience, Veracyte, CURE51, Apmonia Therapeutics

Travel, Accommodations, Expenses: MSD

Jean-Baptiste Bachet

Honoraria: Amgen, Bayer, Merck Serono, Servier, AstraZeneca, Pierre Fabre, Viatris, MSD Oncology, Takeda

Consulting or Advisory Role: Amgen, Bayer, Merck Serono, Servier, Acobiom, GlaxoSmithKline, BMS, MSD, Incyte, AbbVie, Takeda

Travel, Accommodations, Expenses: Merck Serono, Amgen, Roche, Servier, Sanofi

Louis-Marie Dourthe

Honoraria: Pfizer, Merck Serono, Janssen, AstraZeneca, Bayer

Speakers' Bureau: Janssen, Pfizer, Merck Serono, Bayer

Travel, Accommodations, Expenses: Bayer

Thibault Mazard

Honoraria: Takeda

Consulting or Advisory Role: Pierre Fabre, Merck Serono, Servier, Galapagos NV

Research Funding: Amgen (Inst)

Travel, Accommodations, Expenses: Pierre Fabre, Merck Serono, Sanofi, MSD Oncology

Marine Jary

Consulting or Advisory Role: Incyte

Speakers' Bureau: Pierre Fabre, Servier

Research Funding: Bayer (Inst)

Travel, Accommodations, Expenses: Pierre Fabre, Bayer, Roche, Servier, BMSi, Merck, Sanofi, Experf, Ax'Perf, AstraZeneca, Amgen

Clélia Coutzac

Honoraria: Servier, Amgen, Merck Serono, Bristol Myers Squibb, AstraZeneca/Daiichi Sankyo, MSD Oncology

Consulting or Advisory Role: Servier, Amgen, Bristol Myers Squibb

Speakers' Bureau: Servier, Merck Serono, Amgen

Travel, Accommodations, Expenses: Servier, Amgen, Mundipharma, Bristol Myers Squibb, Sandoz

Cédric Lecaille

Travel, Accommodations, Expenses: Servier, Amgen, BMS

Josep Tabernero

Stock and Other Ownership Interests: Oniria Therapeutics, Alentis Therapeutics, 1TRIALSP, Pangaea Oncology

Consulting or Advisory Role: Boehringer Ingelheim, Lilly, MSD, Novartis, Taiho Pharmaceutical, Peptomyc, Chugai Pharma, Pfizer, AstraZeneca, Genentech, Menarini, Servier, F. Hoffmann LaRoche, Pierre Fabre, Daiichi Sankyo, Merus, Scandion Oncology, Sotio, Scorpion Therapeutics, Tolremo, Takeda Pharmaceuticals International AG, Alentis Therapeutics, Quantro Therapeutics, Accent Therapeutics, Ono Pharmaceutical

Côme Lepage

Honoraria: Amgen, Pierre Fabre, Takeda, Servier, Deciphera

Consulting or Advisory Role: Advanced Accelerator Applications

Travel, Accommodations, Expenses: Pierre Fabre, Merck Serono, Astellas Pharma

Jean-François Emile

Honoraria: Bristol Myers Squibb, MSD Oncology, HalioDx, Pierre Fabre, Amgen, Novartis, Merck Serono, Recordati, Qiagen, Deciphera, AstraZeneca

Research Funding: Roche (Inst)

Travel, Accommodations, Expenses: MSD Oncology

Aurélien de Reyniès

Stock and Other Ownership Interests: Minos Biosciences

Consulting or Advisory Role: Qlucore

Uncompensated Relationships: OncoDiag

Julien Taieb

Consulting or Advisory Role: Roche, Merck KGaA, Amgen, Servier, MSD, Pierre Fabre, Novartis, AstraZeneca, BMS, Takeda, Astellas Pharma

Speakers' Bureau: Servier, Amgen, Merck, MSD, Pierre Fabre

Pierre Laurent-Puig

Stock and Other Ownership Interests: Methys

Honoraria: Amgen, AstraZeneca, Merck, Roche, Sanofi, Biocartis, MSD Oncology

Consulting or Advisory Role: Merck, Bristol Myers Squibb, Boehringer Ingelheim

Patents, Royalties, Other Intellectual Property: Inventor of mir31-3p license to IntegraGen

Travel, Accommodations, Expenses: Roche, Merck

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Trial flow diagrams. FFPE, formalin-fixed, paraffin-embedded; RNAseq, RNA sequencing.
FIG 2.
FIG 2.
Kaplan-Meier curves for TTR according to the quartile of the simple/extended prognostic model value in PETACC-8 and IDEA-France cohorts. (A) TTR according to the quartile of Simple Prognostic Model value in the PETACC-8 cohort. (B) TTR according to the quartile of Simple Prognostic Model value in the IDEA-France cohort. (C) TTR according to the quartile of the Extended Prognostic Model value in the PETACC-8 cohort. (D) TTR according to the quartile of the Extended Prognostic Model value in the IDEA-France cohort. HR, hazard ratio; ref, reference; TTR, time to recurrence.
FIG 3.
FIG 3.
Kaplan-Meier curves for TTR according to IPS score in PETACC-8 and IDEA-France cohorts. (A) TTR according to IPS score in the PETACC-8 cohort. (B) TTR according to IPS score in the IDEA-France cohort. HR, hazard ratio; IPS, Immune Proliferative Stromal; ref, reference; TTR, time to recurrence.
FIG 4.
FIG 4.
Kaplan-Meier curves for TTR according to IPS score and ctDNA in the IDEA-France cohort. ctDNA, circulating tumor DNA; IPS, Immune Proliferative Stromal; TTR, time to recurrence.
See this image and copyright information in PMC

References

    1. Grothey A, Venook AP: Optimizing adjuvant therapy for localized colon cancer and treatment selection in advanced colorectal cancer. J Natl Compr Cancer Netw 16:611-615, 2018 - PubMed
    1. Argilés G, Tabernero J, Labianca R, et al. : Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 31:1291-1305, 2020 - PubMed
    1. Sinicrope FA, Huebner LJ, Laurent-Puig P, et al. : Relative contribution of clinical and molecular features to outcome within low and high risk T and N groups in stage III colon cancer (CC). J Clin Oncol 37, 2019. (suppl 15; abstr 3520)
    1. Taieb J, Le Malicot K, Shi Q, et al. : Prognostic value of BRAF and KRAS mutations in MSI and MSS stage III colon cancer. J Natl Cancer Inst 109:djw272, 2017 - PMC - PubMed
    1. Pagès F, Mlecnik B, Marliot F, et al. : International validation of the consensus Immunoscore for the classification of colon cancer: A prognostic and accuracy study. Lancet 391:2128-2139, 2018 - PubMed

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