Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARγ signalling pathway.

BACKGROUND

Cholangiocarcinoma is a devastating cancer with a poor prognosis. Previous reports have presented conflicting results on the role of transforming growth factor-β-induced protein (TGFBI) in malignant cancers. Currently, our understanding of the role of TGFBI in cholangiocarcinoma is ambiguous. The aim of the present study was to investigate the role of TGFBI in human cholangiocarcinoma.

METHODS

Iterative patient partitioning (IPP) scoring and consecutive elimination methods were used to select prognostic biomarkers. mRNA and protein expression levels were determined using Gene Expression Omnibus (GEO), Western blot and ELISA analyses. Biological activities of selected biomarkers were examined using both in vitro and in vivo assays. Prognostic values were assessed using Kaplan-Meier and Liptak's z score analyses.

RESULTS

TGFBI was selected as a candidate cholangiocarcinoma biomarker. GEO database analysis revealed significantly higher TGFBI mRNA expression levels in cholangiocarcinoma tissues compared to matched normal tissues. TGFBI protein was specifically detected in a soluble form in vitro and in vivo. TGFBI silencing evoked significant anti-cancer effects in vitro. Soluble TGFBI treatment aggravated the malignancy of cholangiocarcinoma cells both in vitro and in vivo through activation of the integrin beta-1 (ITGB1) dependent PPARγ signalling pathway. High TGFBI expression was associated with a poor prognosis in patients with cholangiocarcinoma.

CONCLUSIONS

Our data suggest that TGFBI may serve as a promising prognostic biomarker and therapeutic target for cholangiocarcinoma.