Evaluation of HMGB1 Expression as a Clinical Biomarker for Cholangiocarcinoma

Background/Aim: Cholangiocarcinoma (CCA) is an epithelial malignancy that is most prevalent in Southeast Asia, particularly in the northeast of Thailand. Identifying and establishing specific biomarkers of CCA is crucial for ensuring accurate prognosis and enabling effective treatment. High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that can be released by dead or injured cells and is associated with tumor progression. This study aimed to investigate the expression levels of HMGB1 in CCA. Materials and Methods: The clinical significance of HMGB1 levels was assessed by examining their correlation with patients' clinicopathological data. A bioinformatics analysis was conducted to examine HMGB1 mRNA expression and perform survival analysis. The expression levels of 137 tissue cases were evaluated using the immunohistochemical technique, whereas the serum levels of 31 cases were evaluated using indirect ELISA. Results: The GEPIA analysis demonstrated that HMGB1 exhibited elevated mRNA expression in CCA compared to the normal group. Immunohistochemical staining revealed that HMGB1 expression was primarily localized in the nucleus. High HMGB1 expression was observed in 57.6% of tissue samples, while low expression was detected in 42.4%. There was a significant positive correlation between high HMGB1 expression and the extrahepatic type of CCA as well as lymph node metastasis. The measurement of HMGB1 levels were assessed using indirect ELISA in 31 CCA serum samples, where 51.6% exhibited elevated concentrations of HMGB1. Elevated serum HMGB1 levels were significantly associated with advanced tumor stages and high levels of bilirubin levels. Conclusion: HMGB1 in both tissue biopsies and blood serum shows potential as a predictive biomarker in CCA patients. These biomarkers could form the basis for facilitating more effective treatment planning.