Tumour and stroma RNA signatures predict more accurately distant recurrence than clinicopathological factors in resected pancreatic adenocarcinoma

Autor: Jean-Baptiste Bachet, Jean-François Emile, Jean-Luc Van Laethem, Pascal Hammel, Tatjana Arsenijevic, Jérémy Augustin, Francesco Puleo, Rémy Nicolle, Magali Svrcek, Marc Hilmi, Jérôme Cros
Přispěvatelé: (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AstraZeneca Celgene Halozyme, J.B.B. is member of a board and/or received fees from Amgen, AstraZeneca, Bayer, Celgene, Merck Serono, Mundipharma, Pierre Fabre, Roche, Sanofi, Shire, and Servier. P.H. received financial support from AstraZeneca , Celgene , Halozyme , Erythec , Fibrogen , and Rafael . Other authors declare no potential conflicts of interest.
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: European Journal of Cancer
European Journal of Cancer, Elsevier, 2021, 148, pp.171-180. ⟨10.1016/j.ejca.2021.01.042⟩
European journal of cancer, 148
ISSN: 0959-8049
DOI: 10.1016/j.ejca.2021.01.042⟩
Popis: International audience; Background: Few patients with pancreatic adenocarcinoma (PAC) are eligible for surgery. Patients with early relapse have a poor prognosis and might be better candidates for a medical approach. Clinical and pathological parameters only partially predict recurrence and are only obtained after surgery. PAC subtypes based on gene expression were proposed, and we assessed if they could predict the risk and type of recurrence independently of clinicopathological parameters. Methods: Patients with curative-intent surgery for PAC without pretreatment were selected and divided into two independent cohorts defined as discovery (n = 381) and validation (n = 149) cohorts. Transcriptomic analyses were performed on formalin-fixed paraffin-embedded surgical samples to characterise tumour and stroma compartments using previously defined signatures. We associated molecular and clinicopathological characteristics with general, distant, and local recurrences using Cox regression analyses. Results: We found that tumour biology predicted distant recurrence contrary to local recurrence, which was directly related to resection margin status. Pure basal-like and stroma-activated subtypes were strongly associated with distant recurrence, independently of clinicopathological factors (hazard ratios [HRs] = 5.85, p < 0.001 and HR = 1.75, p = 0.007, respectively). By dissecting tumoural and stromal compartments, we demonstrated that the basal-like tumour component positively correlated with distant recurrence in both cohorts (HR = 1.45, p < 0.001 and HR = 1.90, p < 0.001), whereas the inactive structural stroma component was protective against distant recurrence (HR = 0.68, p < 0.001 and HR = 0.72, p < 0.001). Conclusions: In addition to suggesting a different mechanism for local and distant relapse (incomplete resection and high metastatic potential, respectively), our results show the potency of molecular phenotype to predict patient outcome regarding distant recurrences.
Databáze: OpenAIRE
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