Cystatin B Promotes the Proliferation, Migration, and Invasion of Intrahepatic Cholangiocarcinoma

TL;DR

This study shows that Cystatin B promotes the growth and spread of intrahepatic cholangiocarcinoma, suggesting it could be a new target for treatment.

Contribution

The study identifies Cystatin B as a novel driver of intrahepatic cholangiocarcinoma progression through experimental and clinical validation.

Findings

CSTB expression is significantly higher in tumor tissues compared to normal tissues in iCCA patients.

Higher CSTB levels correlate with worse prognosis in iCCA patients.

Knockdown of CSTB reduces tumor growth in mouse models.

Abstract

Background and Aims: Cystatin B (CSTB) has been demonstrated to play a significant role in the pathogenesis of a number of diseases, including the evolution and progression of multiple cancers. Nevertheless, the function of CSTB in intrahepatic cholangiocarcinoma (iCCA) is yet to be fully elucidated. Methods: By analyzing transcriptome sequencing data from the FU-iCCA cohort, the iCCA-27 cohort, and three public databases, we identified genes associated with iCCA prognosis and selected CSTB as the subject of our study. The expression of CSTB was examined between tumor tissues and adjacent normal tissues obtained from iCCA patients via Western blot analysis. The clinical significance of CSTB was analyzed through immunohistochemical staining of a tissue microarray. Subsequently, the biological effects of CSTB overexpression or knockdown on iCCA cells were evaluated in vitro and in vivo. Results: CSTB expression was markedly elevated in the CCA pathological tissues in comparison to the corresponding adjacent normal tissues. A correlation was identified between higher CSTB expression and poorer patient prognosis in the analysis of 176 iCCA patients. It is noteworthy that overexpression or knockdown experiments demonstrated that CSTB plays a role in the proliferation, migration, and invasion of cells. In subcutaneous tumor models in nude mice, the knockdown of CSTB resulted in smaller tumors in terms of size and weight, and a slower growth rate. Conclusions: CSTB plays a significant function in the regulation of iCCA progression and may serve as a promising biomarker for iCCA.

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