| Abstract [eng] |
Background. Cholangiocarcinoma (CCA) is a malignant tumor arising from the epithelium of intrahepatic or extrahepatic bile ducts. Due to its etiological and morphological heterogeneity, as well as the asymptomatic onset of the disease, early diagnosis of CCA is often challenging, and treatment options are severely limited. The non-specific clinical symptoms caused by tumor mass effect and the similarity of anatomical localization pose additional diagnostic difficulties in differentiating distal cholangiocarcinoma (dCCA), pancreatic ductal adenocarcinoma (PDAC), and other malignant or benign periampullary conditions. Currently used diagnostic methods - radiological imaging and serum tumor markers (e.g., CA 19-9) - demonstrate limited sensitivity and specificity, thus highlighting the growing need for novel, reliable, and minimally invasive diagnostic approaches. Liquid biopsy (LB) represents one of the most advanced and promising approaches in translational medicine, which allows for the detection of specific tumor biomarkers (e.g., microRNAs (miRNAs)) in body fluids. The integration of CRISPR-Cas systems with liquid biopsy may further enhance the accuracy of early CCA diagnostics, reduce the need for invasive procedures, and ultimately improve patient outcomes. Methods. A comprehensive review of scientific literature published between 2015 and 2025 was conducted using major medical databases (PubMed, Web of Science, Google Scholar, and Embase). The following MeSH terms were used in various combinations: “cholangiocarcinoma,” “liquid biopsy,” “microRNA,” and “CRISPR-Cas.” Original research articles written in English were selected for analysis. Additionally, a theoretical diagnostic protocol utilizing Rolling Circle Amplification-assisted CRISPR-Cas9 cleavage (RACE) is proposed, focusing on miRNA-16 and miRNA-877 in plasma-derived exosomes to reliably differentiate dCCA from PDAC and benign biliary diseases. Results. The literature analysis revealed that LB, particularly the detection of circulating miRNAs in body fluids (e.g., miR-21, miR-16, miR-877), demonstrates high diagnostic accuracy necessary for early CCA detection. When supplemented with innovative CRISPR-Cas technologies, such as the proposed RACE method, diagnostic accuracy could be further improved, facilitating earlier therapeutic decision-making. This is one of the key factors in improving unfavorable patient outcomes. Conclusion. LB, in combination with CRISPR-Cas systems, could significantly contribute to more accurate CCA diagnosis in the future, reducing the need for invasive procedures and improving patient treatment outcomes. Nevertheless, these methods remain experimental and require thorough clinical validation and standardization before being widely implemented in routine clinical practice. |
