HKDC1 enhances the proliferation, migration and glycolysis of pancreatic adenocarcinoma and is linked to immune infiltration.

ABSTRACT

Background: Understanding the molecular mechanisms of pancreatic adenocarcinoma (PAAD) development is vital for treating this disease, as the current prognosis and treatment options are highly discouraging. Objective: This study aimed to examine the involvement of Hexokinase Domain Containing 1 (HKDC1) in the progression of PAAD. Methods: The study utilized bioinformatics techniques to evaluate the relationship between the expression of HKDC1 and clinical characteristics. In vitro experiments were conducted to investigate the molecular mechanisms and biological functions of HKDC1 in PAAD. Results: The findings of this research indicate that the expression of HKDC1 was increased in various types of human cancers, and a significant correlation was observed between elevated HKDC1 expression in PAAD and unfavorable prognosis. According to the findings from univariate and multivariate Cox regression analyses, HKDC1 could potentially serve as a standalone prognostic indicator for individuals diagnosed with PAAD. After performing calculations, we determined that the HKDC1 high-expression group exhibited lower immunologic score and higher ESTIMATE score, indicating a difference in immune infiltration score. In order to validate the expression of HKDC1 in PAAD cell lines, we analyzed the PAAD cell lines through qPCR and protein blotting. The expression of HKDC1 in human PAAD tissues was also detected by western blotting. Additionally, we explored the involvement of HKDC1 in PAAD by conducting experiments such as colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, and wound healing assays. In our study, we discovered that disruption of HKDC1 expression in PAAD cell types resulted in a decrease in cell growth rate and inhibited cell movement and invasion. Conclusion: To conclude, our findings indicate that HKDC1 has a significant impact on the tumor microenvironment (TME) of PAAD and could potentially be a promising target for PAAD treatment, offering fresh perspectives on the management of PAAD.