Transforming growth factor-β-induced protein (TGFBI) has been identified as a possible biomarker and therapeutic target in cholangiocarcinoma, according to a new study published in Cell Oncology.

The research team employed Gene Expression Omnibus analysis to determine that cholangiocarcinoma tissues had significantly higher TGBFI mRNA expression than healthy matched tissues.

“The insidious presentation of cholangiocarcinoma combined with its aggressive malignant nature and obstinate refractoriness to chemotherapy leads to a notorious high mortality rate, representing up to 2% of all cancer-related deaths worldwide yearly, which prompted us to exploit an effective soluble-biomarker for diagnosis and prognosis,” the authors said.


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“We found that cholangiocarcinoma cells specifically secrete a soluble form of TGFBI compared to the insoluble form produced by other malignant cancers such as hepatocellular and pancreatic cancer.”

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TGFBI has already been identified as a tumor suppressor or oncogene in various cancer types. The research team determined that in vitro silencing of TGFBI expression had significant anticancer effects, while malignancy was induced in cholangiocarcinoma cells via exogenous treatment with soluble TGBFI.

Furthermore, both in vitro and in vivo, they determined that malignancy was included via activation of the integrin beta-1-dependent peroxisome proliferator-activated receptor-y signaling pathway and that high TGFBI expression aggravated the prognosis of patients with cholangiocarcinoma compared with patients with low TGFBI expression.

The generally poor prognosis for cholangiocarcinoma combined with the invasive nature of its diagnosis has led to a search for soluble biomarkers to improve its detection and reduce treatment delays. The identification of TGFBI as a notable prognostic biomarker in cholangiocarcinoma offers the possibility of a new therapeutic target in this disease.

Reference

Lee J, Lee J, Sim W, et al. Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARγ signalling pathway. Cell Oncol (Dordr). Published online March 31, 2022. doi:10.1007/s13402-022-00668-7