Prognostic biomarkers for cholangiocarcinoma (CCA): state of the art

ABSTRACT

Introduction:Although advances in understanding the molecular basis of cholangiocarcinoma (CCA) have been made, surgery is the only curative therapy option and the overall prognosis of patients suffering from the disease remains poor. Therefore, estimation of prognosis based on known and novel biomarkers is essential for therapy guidance of CCA in both, curative and palliative settings.

Areas covered:An extensive literature search on biomarkers for CCA with special emphasis on prognosis was performed. Based on this, prognostic biomarkers from serum, tumor tissue and other compartments that are currently in use or under evaluation for CCA were summarized in this review. Furthermore, an overview of new biomarkers was provided including those determined from extracellular vesicles (EVs), metabolites and nucleic acids. Finally, prognostic markers associated with potential new therapy options for the treatment of CCA were summed up.

Expert opinion:So far, an optimal prognostic biomarker for CCA has not been described. However, based on the increasing knowledge about the molecular basis of CCA but also due to novel, innovative technologies, a plethora of novel prognostic biomarkers is currently under evaluation and will be available for CCA in future.

KEYWORDS:

• Cholangiocarcinoma
• prognosis
• biomarker
• CA19-9
• tumor tissue
• proteins
• miRNAs
• inflammatory/immune cell infiltration
• sarcopenia

Article highlights

• CA19-9 is still the most commonly used prognostic biomarker in CCA

• NLR, PLR, SII and sarcopenia can be easily calculated and add further prognostic information. Similarly, other tumor markers (CYFRA21-1, CEA) can be utilized to estimate the prognosis of patients with CCA

• Assessment of certain markers from tumor tissue can have prognostic (e.g. kras, TP53 mutations), but also therapeutic (FGFR2, IDH-1/-2 alteration) implications for CCA

• miRNAs (e.g. miR21) have proven their value as prognostic biomarkers but are not in routine clinical use so far

• Novel biomarkers from technical advances such as cf-DNA, EVs, CTCs and metabolic profiling are interesting for both prognostic assessment and therapy planning, but their value has to be determined in future trials

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

S A Lang receives research funding from the German Research Council (Deutsche Forschungsgemeinschaft, DFG; FOR2127). U P Neumann gives talks and acts as research/study consultant for Lilly, Roche, Falk and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.