Low Hepsin Expression Associates with a Better Response to Gemcitabine-Based Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma

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INTRODUCTION: Hepsin is a type 2 transmembrane serine protease, primarily located on the cell membrane, which can degrade the extracellular matrix and modify connections between cells and the extracellular matrix. Given these features, hepsin is thought to play a role in cancer invasion and metastasis. While studied in various other cancers, hepsin's role in pancreatic cancer remains unexamined. METHODS: Our study included 223 patients diagnosed with pancreatic ductal adenocarcinoma. Among these, 66 received neoadjuvant therapy and these were analyzed separately. Tissue microarrays and immunohistochemistry were used to assess the expression of hepsin in pancreatic ductal adenocarcinoma tissue. Hepsin expression intensity, ranging from negative to strong, was evaluated against clinicopathological parameters, including age at surgery, sex, T-stage, N-stage, tumor grade, perivascular and perineural invasion, CA19-9 levels, ASA class, stage, and, in the neoadjuvant-treated group, response to neoadjuvant therapy. RESULTS: A strong hepsin expression was observed in 105 (67%) patients who did not receive neoadjuvant therapy, while 27 (42%) neoadjuvant-treated patients exhibited a strong expression. Hepsin expression did not associate with survival in either group. In the neoadjuvant-treated group, a strong positivity was, however, associated with a lower T-stage (p = 0.005) and higher N-stage (p = 0.048). Among those receiving gemcitabine-based chemotherapy, a weaker hepsin expression was associated with a better treatment response (p = 0.011). CONCLUSIONS: A low hepsin expression following neoadjuvant therapy is associated with a better treatment response among those receiving gemcitabine-based treatment. Thus, hepsin does not appear to influence prognosis in pancreatic cancer patients, regardless of whether they received neoadjuvant therapy or not.

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