Cohort study reveals improved survival with high MMP-8 expression in pancreatic cancer patients responding to neoadjuvant therapy, highlighting its role as a conditional protective biomarker.
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.
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Kesti et al. (2025) studied this question.
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