Researchers have discovered that serum thrombospondin-2 (THBS2) can combine with carbohydrate antigen (CA) 19-9 to serve as a potential biomarker combination for distal cholangiocarcinoma (dCCA) and pancreatic ductal adenocarcinoma (PDAC), according to a study published in Clinical and Transatlantic Oncology.

The most important clinical implication of this study is that THBS2 can be used with CA 19-9 to identify those diseases early — while curative treatment remains possible.

Cholangiocarcinoma (CCA) refers to a rare group of cancers that originate from the biliary tree, which represent about 3% of gastrointestinal cancers. CCAs usually carry a poor prognosis due to late diagnosis. The 2 cancers this study is focused on share similar features. The anatomical location of dCCA is between the cystic duct insertion and the ampulla of Vater, making it very close to the pancreas. This makes it difficult for surgeons to differentiate between the 2 until resection and histopathological evaluation have been performed. 

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Read more about CCA epidemiology

Currently, CA 19-9 is the only biomarker for dCCA and PDAC. CA 19-9 has limited sensitivity and specificity in the early stages, making it more suitable to chart disease progression in the later stages. As for THBS2, research has shown that it can be an excellent biomarker for PDAC, differentiating it from benign conditions like chronic pancreatitis. The purpose of this study was to evaluate the usefulness of THBS2 as a diagnostic and prognostic biomarker for dCCA and PDAC when used in combination with CA 19-9. 

Researchers collected serum samples from healthy donors (n=52), as well as patients who underwent pancreatic surgery for dCCA (n=51), PDAC (n=52), and benign pancreatic diseases (n=27) in Skåne University Hospital, Malmö, Sweden between 2012 and 2019. The THBS2 levels from the serum samples collected were then determined by an enzyme-linked immunosorbent assay. 

Researchers found that THBS2 levels were similar in both dCCA and PDAC compared to the control group. However, the combination of THBS2 and CA 19-9 was superior in differentiating dCCA and PDAC from healthy donors compared to just CA 19-9 alone. The diagnostic value of this combination of biomarkers is even greater in earlier stages of the disease.

“Further research is needed to understand the expression of THBS2 in different malignant and benign conditions as well as assay development prior to clinical use,” the authors of the study concluded. 


Byrling J, Hilmersson KS, Ansari D. et al. Thrombospondin-2 as a diagnostic biomarker for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. Clin Transl Oncol. Published online July 28, 2021. doi:10.1007/s12094-021-02685-8