Diagnostic and prognostic biomarkers in cholangiocarcinoma

Abstract

The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non‐invasive approaches able to accurately detect this silent tumour at early stages, when therapeutic options can be potentially curative or may at least increase the overall survival of patients. The fact that the majority of CCA tumours are not linked to any known aetiological factor highly compromises the monitoring of patients at risk for tumour development and also their early diagnosis. Combination of clinical/biochemical features, imaging techniques and analysis of non‐specific tumour biomarkers in serum are commonly used to help in the diagnosis of CCA, but tumour biopsy is usually required to confirm the diagnosis. Moreover, no prognostic biomarkers are currently used in the clinical setting, deserving more innovative research, and international validation and consensus. Important efforts have been made in the last few years to identify accurate non‐invasive biomarkers, by using innovative techniques and high‐throughput omics technologies. This review summarizes and discusses the advances in the investigation of novel diagnostic and prognostic biomarkers in CCA and envisions the future directions in this field of research.

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

“…In the last decade, a considerable effort has been made to identify novel non-invasive biomarkers for the early and accurate diagnosis of CCA [7]. Here, we report for the first time the differential RNA profile of serum and urine EVs from patients with CCA, PSC, or UC, and healthy individuals, identifying new potential biomarkers with high diagnostic capacity.…”

“…Similarly, the levels of the long non-coding RNA prostate cancer associated 3 (PCA3) were abundantly found in urine of patients with prostate cancer, constituting a promising non-invasive biomarker for the diagnosis of that cancer [37,38]. the levels of several miRNAs were also reported altered in serum, plasma, and urine of patients with gastrointestinal cancers, including CCA, constituting also potential novel biomarkers for cancer diagnosis [7,33,[39][40][41].…”

“…the diagnosis of CCA is usually conducted by combining clinical, biochemical, radiological, and histological information. Imaging techniques usually rely on computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), positron emission tomography (PET), percutaneous transhepatic cholangiography (PTC), endoscopic retrograde cholangiopancreatography (ERCP), or endoscopic ultrasound depending on the tumor location [1,5,7]. However, imaging proceedings have important limitations, as they are not accurate enough to determine the malignity of the tumor masses, particularly in early stages, as well as to differentiate between the main primary liver cancers, i.e., iCCA, hepatocellular carcinoma (HCC) or HCC-CCA mixed tumors, which is fundamental to provide the appropriate standards of care.…”

“…On the other hand, MRCP and histological analysis (biopsy or brushing cytology) comprise the major diagnostic tools for PSC [4,8,9]. In addition, the measurement of non-specific serum tumor biomarkers [i.e., carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA)] is commonly conducted in order to help in the diagnosis of CCA, but their low sensitivity (particularly in early stages of the disease) and specificity (also elevated in some PSC patients without cancer), raise important concerns regarding their clinical utility [7,10]. Therefore, tumor biopsy is currently mandatory to confirm the diagnosis and staging of CCA, guiding the clinical management of these patients [11].…”

A novel mouse model of cholangiocarcinoma uncovers a role for a SOX17-Tensin 4 pathway in tumor progression

“…Since this results in part from delayed diagnosis, there is a need to understand the mechanisms that drive development of precancerous lesions and their progression towards malignant tumor. 1 A range of perturbed signaling pathways and genomic alterations was found to be associated with late-stage cholangiocarcinoma, but there is still limited knowledge about how such pathways and mutations evolve throughout tumorigenesis. [2][3][4][5][6][7][8] Moreover, our understanding of this process is further complicated by the observation that iCCA can arise from several cell types, namely cholangiocytes, hepatocytes, progenitor cells and peribiliary glands.…”