OncoImmunology (Jan 2020)

MMP2 as an independent prognostic stratifier in oral cavity cancers

  • Caroline Hoffmann,
  • Sophie Vacher,
  • Philémon Sirven,
  • Charlotte Lecerf,
  • Lucile Massenet,
  • Aurélie Moreira,
  • Aurore Surun,
  • Anne Schnitzler,
  • Jerzy Klijanienko,
  • Odette Mariani,
  • Emmanuelle Jeannot,
  • Nathalie Badois,
  • Maria Lesnik,
  • Olivier Choussy,
  • Christophe Le Tourneau,
  • Maude Guillot-Delost,
  • Maud Kamal,
  • Ivan Bieche,
  • Vassili Soumelis

DOI
https://doi.org/10.1080/2162402X.2020.1754094
Journal volume & issue
Vol. 9, no. 1

Abstract

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Background Around 25% of oral cavity squamous cell carcinoma (OCSCC) are not controlled by the standard of care, but there is currently no validated biomarker to identify those patients. Our objective was to determine a robust biomarker for severe OCSCC, using a biology-driven strategy. Patients and methods Tumor and juxtatumor secretome were analyzed in a prospective discovery cohort of 37 OCSCC treated by primary surgery. Independent biomarker validation was performed by RTqPCR in a retrospective cohort of 145 patients with similar clinical features. An 18-gene signature (18 G) predictive of the response to PD-1 blockade was evaluated in the same cohort. Results Among 29 deregulated molecules identified in a secretome analysis, including chemokines, cytokines, growth factors, and molecules related to tumor growth and tissue remodeling, only soluble MMP2 was a prognostic biomarker. In our validation cohort, high levels of MMP2 and CD276, and low levels of CXCL10 and STAT1 mRNA were associated with poor prognosis in univariate analysis (Kaplan-Meier). MMP2 (p = .001) and extra-nodal extension (ENE) (p = .006) were independent biomarkers of disease-specific survival (DSS) in multivariate analysis and defined prognostic groups with 5-year DSS ranging from 36% (MMP2highENE+) to 88% (MMP2lowENE-). The expression of 18 G was similar in the different prognostic groups, suggesting comparable responsiveness to anti-PD-1. Conclusion High levels of MMP2 were an independent and validated prognostic biomarker, surpassing other molecules of a large panel of the tumor and immune-related processes, which may be used to select poor prognosis patients for intensified neoadjuvant or adjuvant regimens.

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