Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface

Abstract Background Tumor Budding (TB) and Immunoscore are independent prognostic markers in colon cancer (CC). Given their respective representation of tumor aggressiveness and immune response, we examined their combination in association with patient disease-free survival (DFS) in pTNM stage I-III...

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Main Authors: T. S. Haddad, J. M. Bokhorst, M. D. Berger, L. v. d. Dobbelsteen, F. Simmer, F. Ciompi, J. Galon, J. v. d. Laak, F. Pagès, I. Zlobec, A. Lugli, I. D. Nagtegaal
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Language:English
Published: BMC 2024-12-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-024-05818-z
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author T. S. Haddad
J. M. Bokhorst
M. D. Berger
L. v. d. Dobbelsteen
F. Simmer
F. Ciompi
J. Galon
J. v. d. Laak
F. Pagès
I. Zlobec
A. Lugli
I. D. Nagtegaal
author_facet T. S. Haddad
J. M. Bokhorst
M. D. Berger
L. v. d. Dobbelsteen
F. Simmer
F. Ciompi
J. Galon
J. v. d. Laak
F. Pagès
I. Zlobec
A. Lugli
I. D. Nagtegaal
author_sort T. S. Haddad
collection DOAJ
description Abstract Background Tumor Budding (TB) and Immunoscore are independent prognostic markers in colon cancer (CC). Given their respective representation of tumor aggressiveness and immune response, we examined their combination in association with patient disease-free survival (DFS) in pTNM stage I-III CC. Methods In a series of pTNM stage I-III CCs (n = 654), the Immunoscore was computed and TB detected automatically using a deep learning network. Two-tiered systems for both biomarkers were used with cut-offs of 25% and ten buds for Immunoscore and TB according to clinical guidelines, respectively. Associations of Immunoscore with TB with 5-year DFS were examined using Kaplan–Meier survival analysis in addition to multivariable modeling and relative contribution analysis using Cox regression. Results Immunoscore and TB independently are prognostic with hazard ratio (HR) = 2.0, 95% confidence interval (CI) 1.4–2.8 and HR 2.5, with 95% CI 1.4–4.5, respectively; P value < 0.0001. By combining Immunoscore with TB, patients with Immunoscore Low, TB High tumors had a significantly poorer DFS (HR 5.6, 95% CI 2.6–12.0; P value < 0.0001) than those with Immunoscore High, TB Low tumors. The combined Immunoscore with TB score was independently prognostic (P value = 0.009) in comparison to N-stage, T-stage, and MSI. Immunoscore with TB had the highest relative contribution (35%) to DFS in pTNM stage I-II CCs. Conclusions The association of Immunoscore and TB with patient survival suggests that both biomarkers are complementary and should be interpreted in combination to identify high-risk Stage I-II patients who should be considered for adjuvant therapy or further diagnostic testing.
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spelling doaj-art-ea724b6e50394946b46ce85e3cd9044e2025-08-20T02:20:44ZengBMCJournal of Translational Medicine1479-58762024-12-0122111110.1186/s12967-024-05818-zCombining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interfaceT. S. Haddad0J. M. Bokhorst1M. D. Berger2L. v. d. Dobbelsteen3F. Simmer4F. Ciompi5J. Galon6J. v. d. Laak7F. Pagès8I. Zlobec9A. Lugli10I. D. Nagtegaal11Radboud University Medical CenterRadboud University Medical CenterDepartment of Medical Oncology, Inselspital, Bern University Hospital, University of BernRadboud University Medical CenterRadboud University Medical CenterRadboud University Medical CenterCentre de Recherche Des Cordeliers, Sorbonne Université, Université Paris CitéRadboud University Medical CenterCentre de Recherche Des Cordeliers, Sorbonne Université, Université Paris CitéDepartment of Medical Oncology, Inselspital, Bern University Hospital, University of BernInstitute of Tissue Medicine and Pathology, University of BernRadboud University Medical CenterAbstract Background Tumor Budding (TB) and Immunoscore are independent prognostic markers in colon cancer (CC). Given their respective representation of tumor aggressiveness and immune response, we examined their combination in association with patient disease-free survival (DFS) in pTNM stage I-III CC. Methods In a series of pTNM stage I-III CCs (n = 654), the Immunoscore was computed and TB detected automatically using a deep learning network. Two-tiered systems for both biomarkers were used with cut-offs of 25% and ten buds for Immunoscore and TB according to clinical guidelines, respectively. Associations of Immunoscore with TB with 5-year DFS were examined using Kaplan–Meier survival analysis in addition to multivariable modeling and relative contribution analysis using Cox regression. Results Immunoscore and TB independently are prognostic with hazard ratio (HR) = 2.0, 95% confidence interval (CI) 1.4–2.8 and HR 2.5, with 95% CI 1.4–4.5, respectively; P value < 0.0001. By combining Immunoscore with TB, patients with Immunoscore Low, TB High tumors had a significantly poorer DFS (HR 5.6, 95% CI 2.6–12.0; P value < 0.0001) than those with Immunoscore High, TB Low tumors. The combined Immunoscore with TB score was independently prognostic (P value = 0.009) in comparison to N-stage, T-stage, and MSI. Immunoscore with TB had the highest relative contribution (35%) to DFS in pTNM stage I-II CCs. Conclusions The association of Immunoscore and TB with patient survival suggests that both biomarkers are complementary and should be interpreted in combination to identify high-risk Stage I-II patients who should be considered for adjuvant therapy or further diagnostic testing.https://doi.org/10.1186/s12967-024-05818-zImmunoscoreTumor buddingColon cancerAI
spellingShingle T. S. Haddad
J. M. Bokhorst
M. D. Berger
L. v. d. Dobbelsteen
F. Simmer
F. Ciompi
J. Galon
J. v. d. Laak
F. Pagès
I. Zlobec
A. Lugli
I. D. Nagtegaal
Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface
Journal of Translational Medicine
Immunoscore
Tumor budding
Colon cancer
AI
title Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface
title_full Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface
title_fullStr Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface
title_full_unstemmed Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface
title_short Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface
title_sort combining immunoscore and tumor budding in colon cancer an insightful prognostication based on the tumor host interface
topic Immunoscore
Tumor budding
Colon cancer
AI
url https://doi.org/10.1186/s12967-024-05818-z
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