The search for novel diagnostic and prognostic biomarkers in cholangiocarcinoma

Abstract

The poor prognosis of cholangiocarcinoma (CCA) is in part due to late diagnosis, which is currently achieved by a combination of clinical, radiological and histological approaches. Available biomarkers determined in serum and biopsy samples to assist in CCA diagnosis are not sufficiently sensitive and specific. Therefore, the identification of new biomarkers, preferably those obtained by minimally invasive methods, such as liquid biopsy, is important. The development of innovative technologies has permitted to identify a significant number of genetic, epigenetic, proteomic and metabolomic CCA features with potential clinical usefulness in early diagnosis, prognosis or prediction of treatment response. Potential new candidates must be rigorously evaluated prior to entering routine clinical application. Unfortunately, to date, no such biomarker has achieved validation for these purposes. This review is an up-to-date of currently used biomarkers and the candidates with promising characteristics that could be included in the clinical practice in the next future. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis

“…The analysis of nonspecific biomarkers, such as CA 19‐9, may help in the noninvasive diagnosis of CCA. However, its specificity is low, because this biomarker is also elevated in one third of patients with PSC without biliary cancer, and in other liver diseases and tumors; in addition, there is an important heterogeneity in its elevation in patients with iCCA . Moreover, the sensitivity of this cancer biomarker is compromised by the fact that ~10% of the population does not produce CA 19‐9 .…”

“…However, its specificity is low, because this biomarker is also elevated in one third of patients with PSC without biliary cancer, and in other liver diseases and tumors; in addition, there is an important heterogeneity in its elevation in patients with iCCA. (16) Moreover, the sensitivity of this cancer biomarker is compromised by the fact that ~10% of the population does not produce CA 19-9. (17) On the other hand, AFP provides low diagnostic capacity for HCC and is therefore not recommended for screening or diagnosis in Western guidelines.…”

B7‐H3 expression and its correlation with clinicopathologic features, angiogenesis, and prognosis in intrahepatic cholangiocarcinoma

“…As the effect of adjuvant chemotherapy and adjuvant radiotherapy is limited , surgery is the only potentially curative treatment of cholangiocarcinoma. However, the overall 5‐year survival after resection is usually lower than 40%, while in non‐operable tumors, the overall 5‐year survival is less than 5% . Thus, it is urgent to identify new biomarkers with diagnostic, prognostic, or therapeutic value.…”

Weighted gene coexpression network analysis reveals hub genes involved in cholangiocarcinoma progression and prognosis

“…The fact that CCA has a slow evolution, atypical symptoms, and limited therapeutic measures makes it difficult for early diagnosis and hence most patients are detected only in advanced or metastatic stages. The overall 5‐year survival after resection is usually lower than 40%; in non‐operable CCAs the overall 5‐year survival is less than 5% . Therefore, to establish reliable biomarkers that are specific to the early stages of the disease is needed urgently to overcome the poor prognosis and delayed treatment.…”

“…The overall 5-year survival after resection is usually lower than 40%; in non-operable CCAs the overall 5-year survival is less than 5%. 4 Therefore, to establish reliable biomarkers that are specific to the early stages of the disease is needed urgently to overcome the poor prognosis and delayed treatment.…”