Secretory Leukocyte Protease Inhibitor (SLPI) as a Diagnostic Biomarker and Facilitator of Cell Proliferation in Cholangiocarcinoma
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Abstract
Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor involved in inflammatory processes and has been implicated in various cancers. However, its role in cholangiocarcinoma (CCA) remains unclear. This study aimed to investigate SLPI expression in CCA tissues and serum, and to explore its effect on CCA cell proliferation. Immunohistochemical analysis of 50 CCA samples revealed significantly elevated SLPI expression compared to adjacent normal bile duct (NBD) and hepatocyte tissues (p = 0.00136). High SLPI expression was significantly associated with lymphatic metastasis (p = 0.0312), suggesting its relevance in tumor progression. Serum SLPI levels, measured by ELISA, showed a trend toward increased levels in CCA patients compared to healthy and Opisthorchis viverrini (OV)-infected individuals, with a statistically significant difference between CCA and hepatocellular carcinoma (HCC) patients (p < 0.05). Functional analysis using clonogenic assays demonstrated that treatment with recombinant human SLPI (rhSLPI) enhanced KKU-100 CCA cell survival in a dose-dependent manner, with 10 µg/mL rhSLPI significantly increasing the surviving fraction compared to the control group (p = 0.0064). These findings suggest that SLPI not only serves as a potential biomarker for distinguishing CCA from HCC but also contributes to CCA cell proliferation, highlighting its potential diagnostic and therapeutic relevance.
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