Date Published: January 17, 2019
Publisher: Public Library of Science
Author(s): Sven H. Loosen, Georg Lurje, Georg Wiltberger, Mihael Vucur, Alexander Koch, Jakob N. Kather, Pia Paffenholz, Frank Tacke, Florian T. Ulmer, Christian Trautwein, Tom Luedde, Ulf P. Neumann, Christoph Roderburg, Niklas K. Björkström.
Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy. Despite tremendous research activities, the prognosis for the majority of patients is still poor. Only in case of early diagnosis, liver resection might potentially lead to long-term survival. However, it is still unclear which patients benefit most from extensive liver surgery, highlighting the need for new diagnostic and prognostic stratification strategies.
Serum concentrations of a 4 miRNA panel (miR-122, miR-192, miR-29b and miR-155) were analyzed using semi-quantitative reverse-transcriptase PCR in serum samples from 94 patients with cholangiocarcinoma undergoing tumour resection and 40 healthy controls. Results were correlated with clinical data.
Serum concentrations of miR-122, miR-192, miR-29b and miR-155 were significantly elevated in patients with CCA compared to healthy controls or patients with primary sclerosing cholangitis without malignant transformation. Although preoperative levels of these miRNAs were unsuitable as a prognostic marker of survival, a strong postoperative decline of miR-122 serum levels was significantly associated with a favorable patients’ prognosis.
Analysis of circulating miRNAs represents a promising tool for the diagnosis of even early stage CCA. A postoperative decline in miRNA serum concentrations might be indicative for a favorable patients’ outcome and helpful to identify patients with a good prognosis after extended liver surgery.
Compared to other gastrointestinal cancers, cholangiocarcinoma (CCA) is a comparatively rare malignancy originating from the bile ducts . Besides a relatively high prevalence in some parts of Asia, CCA shows an incidence rate of 2-3/100,000 people in the United states and most parts of Europe . However, the global incidence rates are increasing over the last decades , leading to a progressive awareness of this disease in the field of gastrointestinal oncology. Apart from liver transplantation, surgical tumor resection has remained the only potentially curative treatment option in daily practice but only few patients qualify for surgery due to advanced stage of disease at diagnosis . Thus, early detection of CCA is essential to provide patients with the best possible therapeutic approach in order to improve the patients’ prognosis. However, the scientific effort of the last years have failed to establish appropriate biomarkers for this purpose and the clinically most widely used tumor markers such as CEA and CA19-9 have only a limited diagnostic power [5,6]. Therefore, novel classes of biomarkers are urgently needed in the diagnostics and treatment of patients with CCA.
In the present study, we demonstrate that pre-operative levels of circulating miR-122, miR-192, miR-29b and miR-155 are elevated in patients with cholangiocarcinoma when compared to healthy controls or PSC patients without malignant transformation. Importantly, a strong postoperative decrease of miR-122, when compared to pre-operative levels, was associated with a favorable patients’ prognosis, indicating that the analysis of circulating miRNAs might not only be helpful when performed for diagnostic purposes but also to predict patients’ outcome after extended liver surgery.