Improved detection of cholangiocarcinoma in high risk patients by biomarker analyses of small amounts of bile

From left: HM Vedeld, MM Grimsrud, T Folseraas, GE Lind
From left: HM Vedeld, MM Grimsrud, T Folseraas, GE Lind

Primary sclerosing cholangitis (PSC) is a progressive chronic liver disease associated with increased risk of cholangiocarcinoma; a highly deadly malignancy that arises in the bile ducts. Due to nonspecific presenting features and overlapping findings in malignant and benign disease progression in PSC, the diagnostic accuracy for cholangiocarcinoma in PSC is low. Consequently, cholangiocarcinoma is commonly detected at advanced stage where most patients have a poor chance of surviving, making cholangiocarcinoma the most common cause of death among patients with PSC.

In collaboration with the clinical PSC research group (lead by Trine Folseraas), the Lind lab has analyzed DNA methylation markers in bile from Norwegian, Finish and Swedish cholangiocarcinoma and PSC patients. They demonstrate that the markers can accurately distinguish between patients with cholangiocarcinoma complicated with PSC and PSC alone with a sensitivity of 100% and a specificity of 90%. Importantly, the cholangiocarcinoma samples analysed include early- and late stage cancer, different tumor growth patterns, anatomical locations, and CA 19-9 levels, showing that the markers can detect cholangiocarcinoma irrespective of clinical and molecular features.

If cholangiocarcinoma is detected at an early stage, curative surgical resection or liver transplantation is possible. In patients with unresectable disease, representing the majority of cases at diagnosis, the median survival is less than 12 months. With their high accuracy the biomarkers have potential to complement/improve current detection and surveillance methods for CCA in PSC patients, with a potential high impact on life expectancy.

The results are published in Hepatology. Hege Marie Vedeld and Marit Mæle Grimsrud are shared first authors, and Guro Lind is corresponding author.

Hepatology. 2021 Aug 26. doi: 10.1002/hep.32125. Online ahead of print. PMID: 34435693

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