The prognostic significance of MMP-8 tissue Immunoexpression in pancreatic ductal adenocarcinoma after neoadjuvant therapy - UTU Research Portal

A1 Refereed original research article in a scientific journal

The prognostic significance of MMP-8 tissue Immunoexpression in pancreatic ductal adenocarcinoma after neoadjuvant therapy

Authors: Kesti, Ella; Eurola, Annika; Kaasinen, Mirjami; Mustonen, Harri; Hagström, Jaana; Sorsa, Timo; Ristimäki, Ari; Seppänen, Hanna; Haglund, Caj; Sund, Malin

Publisher: NATURE PORTFOLIO

Publishing place: BERLIN

Publication year: 2025

Journal: Scientific Reports

Journal name in source: SCIENTIFIC REPORTS

Journal acronym: SCI REP-UK

Article number: 24719

Volume: 15

Issue: 1

Number of pages: 12

eISSN: 2045-2322

DOI: https://doi.org/10.1038/s41598-025-10538-5

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Open Access publication channel

Web address : https://www.nature.com/articles/s41598-025-10538-5

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/499383604

Self-archived copy's licence: CC BY NC ND

Self-archived copy's version: Publisher`s PDF

Abstract

Neoadjuvant therapy (NAT) has become increasingly common in pancreatic ductal adenocarcinoma (PDAC). Still, PDAC remains one of the deadliest cancers and clinically useful biomarkers are needed. Matrix metalloproteinase 8 (MMP-8) has previously been identified as a potential biomarker for PDAC patients undergoing up-front surgery. We investigated the prognostic significance of MMP-8 in PDAC patients treated with NAT and evaluated the association of MMP-8 expression to treatment response. We studied MMP-8 expression using immunohistochemistry in a tissue microarray with samples from 115 NAT and 144 up-front surgery patients. We examined NAT response from resection specimens by estimating the amount of residual tumour cells. We analysed the association of MMP-8 immunoexpression with survival and treatment response. High MMP-8 immunoexpression associated with better survival among patients with strong NAT response (HR 0.22, CI95% 0.05-0.86, p = 0.030). This association was not observed among patients with poor NAT response nor in the overall NAT group. Furthermore, MMP-8 expression did not differ significantly between the NAT and up-front surgery groups. In conclusion, the MMP-8 tissue expression after NAT is a protective biomarker in PDAC patients with strong NAT response but fails to associate with favourable prognosis in patients with poor NAT response.

Keywords:

Matrix metalloproteinase 8, Neoadjuvant therapy, PDAC

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Funding information in the publication:
Open access funded by Helsinki University Library. This work was supported by grants from Finska Läkaresällskapet [to EK, HS, CH and MS]; Orion Research Foundation sr [to EK]; the Sigrid Jusélius Foundation [to HS, CH and MS]; Academy of Finland [to HS]; Finnish State Subsidy fund [to HS]; the Cancer Foundation Finland [to HS]; the Swedish Research Council [2019 − 01690, to MS], the Swedish Cancer Society [19 0273, to MS], the Sjöberg Foundation [to MS], Medicinska Understöodsföreningen Liv och Hälsa [to MS]. The funders had no control on content of the manuscript or in decision to publish.