Highlights
- •RNA signatures predict distant relapse better than clinicopathological factors.
- •Basal-like tumour component is associated with more distant recurrence.
- •Inactive structural stroma component is protective against distant recurrence.
- •Local relapse depends on resection margins, independently of tumour biology.
Abstract
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.
Keywords
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Article info
Publication history
Published online: March 18, 2021
Accepted:
January 29,
2021
Received in revised form:
January 19,
2021
Received:
October 8,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
