Kesti Ella, Eurola Annika, Kaasinen Mirjami, Mustonen Harri, Hagström Jaana, Sorsa Timo, Ristimäki Ari, Seppänen Hanna, Haglund Caj, Sund Malin
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, 00290, Finland.
University of Helsinki, Helsinki University Hospital, Stenbäckinkatu 9 A 3, P.O. Box 440, Helsinki, FIN-00029 HUS, Finland.
Sci Rep. 2025 Jul 9;15(1):24719. doi: 10.1038/s41598-025-10538-5.
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.
新辅助治疗（NAT）在胰腺导管腺癌（PDAC）中已变得越来越普遍。尽管如此，PDAC仍然是最致命的癌症之一，因此需要临床可用的生物标志物。基质金属蛋白酶8（MMP - 8）先前已被确定为接受 upfront 手术的PDAC患者的潜在生物标志物。我们研究了MMP - 8在接受NAT治疗的PDAC患者中的预后意义，并评估了MMP - 8表达与治疗反应的相关性。我们在一个组织微阵列中使用免疫组织化学研究了MMP - 8的表达，该微阵列包含来自115例接受NAT治疗的患者和144例接受 upfront 手术的患者的样本。我们通过估计残余肿瘤细胞的数量来检查切除标本的NAT反应。我们分析了MMP - 8免疫表达与生存及治疗反应的相关性。在NAT反应强烈的患者中，高MMP - 8免疫表达与更好的生存率相关（HR 0.22，CI95% 0.05 - 0.86，p = 0.030）。在NAT反应较差的患者中以及在整个NAT组中均未观察到这种相关性。此外，NAT组和 upfront 手术组之间的MMP - 8表达没有显著差异。总之，NAT后MMP - 8的组织表达在NAT反应强烈的PDAC患者中是一种保护性生物标志物，但在NAT反应较差的患者中与良好预后无关。
