Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini (original) (raw)
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The miRNAome of Opisthorchis viverrini induced intrahepatic cholangiocarcinoma
Genomics Data, 2014
Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer, arising in the biliary ducts that extend into the liver. The highest incidence of ICC occurs in Southeast Asia, particularly in the Mekong River Basin countries of Thailand, Laos, Cambodia, and Vietnam, where it is strongly associated with chronic infection by the food-borne liver fluke Opisthorchis viverrini (OV), one of only three eukaryote pathogens considered Group one carcinogens. Intrahepatic cholangiocarcinoma is usually diagnosed at an advanced stage, with a poor prognosis and survival often less than 24 months. Hence, biomarkers that enable the early detection of ICC would be desirable and have a potentially important impact on the public health in the resource-poor regions where this cancer is most prevalent.. As microRNAs (miRNAs) remain well preserved after formalin fixation, there is much interest in developing them as biomarkers that can be investigated using tumor biopsy samples preserved in formalin fixed paraffin embedded (FFPE) tumor blocks. Recently, we reported the first comprehensive profiling of tissue-based miRNA expression using FFPE from the three most common subtypes of OV-induced ICC tumors: moderately differentiated ICC, papillary ICC, and well-differentiated ICC. We observed that each subtype of OV-induced ICC exhibited a distinct miRNA profile, which suggested the involvement of specific sets of miRNAs in the progression of this cancer. In addition, nontumor tissue adjacent to ICC tumor tissue on the same FFPE block shared a similar miRNA dysregulation profile with the tumor tissue than with normal (non-tumor) liver tissue (individuals without ICC or OV infection). Herein, we provide a detailed description of the microarray analysis procedures used to derive these findings.
Journal of hepato-biliary-pancreatic sciences, 2014
This study aimed to investigate the miR-192 levels in patients' sera of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic indicator. MicroRNA polymerase chain reaction (PCR) array was performed using pooled serum samples from 11 CCA patients and nine healthy subjects. Selected miRNAs were verified for the differential levels in both sera and tumor tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using TaqMan miRNA expression assay. Our results demonstrated that miR-192 was significantly higher in the serum of CCA patients than that in healthy subjects giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] = 0.803; 95% confidence interval [CI], 0.708-0.897, P < 0.0001). Serum miR-192 examined in Ov infected subjects and subjects with periductal fibrosis were increased but not statistically significantly when compared with healthy subjects. High levels of serum miR-192 were significantly correlated with l...
The association between circulating MicroRNA‐150 level and cholangiocarcinoma
Journal of Clinical Laboratory Analysis, 2020
Cholangiocarcinoma (CCA) is a rare tumor comprising approximately 3% of gastrointestinal tumors with an overall incidence of less than 2/100 000. It is the second most common primary hepatic malignancy following hepatocellular carcinoma (HCC). 1,2 CCA incidence has been increasing globally during the last decades, where its incidence increases with age. 3 According to the anatomic location, CCA is classified into intrahepatic (IH-CCA) and extrahepatic (EH-CCA) where the later accounts for 80%-90% of all cases. 4 The commonest risk factors for CCA are primary sclerosing cholangitis (PSC), 5 chronic liver disease (including chronic viral hepatitis B and C), 6 and intrahepatic stones (hepatolithiasis). 7 CCA patients remain clinically silent until the advanced stages of the disease. The common clinical feature of EH-CCA is biliary obstruction resulting in painless jaundice, while IH-CCA presents in most cases
MicroRNAs in the Cholangiopathies: Pathogenesis, Diagnosis, and Treatment
Journal of Clinical Medicine, 2015
The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both children and adults. Contributing to this situation is the absence of a thorough understanding of their pathogenesis and a lack of adequate diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that modify gene expression post-transcriptionally. They have been implicated in the pathogenesis of many diseases, including the cholangiopathies. Thus, in this review we provide an overview of the literature on miRNAs in the cholangiopathies and discuss future research directions.
Pharmacogenomics, 2017
Cholangiocarcinoma (CCA) is a lethal malignancy originating from the biliary tract epithelium. Most patients are diagnosed at an advanced stage. Even after resection with curative intent, prognosis remains poor. Previous studies have reported the evolving role of miRNAs as novel biomarkers in cancer diagnosis, prognostication and chemotherapy response. Various miRNAs, such as miR-21, miR-26, miR-122 and miR-150, have been identified as possible blood-based biomarkers for noninvasive diagnosis of CCA. Moreover, epithelial-mesenchymal transition (EMT)- and angiogenesis-associated miRNAs have been implicated in tumor cell dissemination and are able to determine clinical outcome. In fact, miRNAs involved in cell survival might even determine chemotherapy response. This review provides an overview of known miRNAs as CCA-specific biomarkers.
Serum micrornas as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma
Clinical & Experimental Immunology, 2016
Summary The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]. Receiver operating characteristic (ROC) curves were established and only miRNAs with an area under the curve (AUC) > 0·70 were considered useful as biomarkers. In the discovery phase we identified the following: 21 miRNAs expressed differentially in PSC, 33 in CC and 26 in both in comparison to control subjects as well as 24 miRNAs expressed differentially between ...
Cancer management and research, 2018
Several dysregulated microRNAs (miRNAs) have been implicated in the pathogenesis of cholangiocarcinoma (CCA); however, small sample sizes and invariable research designs are limitations, hindering a thorough analysis of miRNAs as diagnostic and prognostic tools for CCA. This study aimed to systematically summarize the clinical value of miRNAs in human CCA both for all available miRNAs and single miRNA with multiple researches. Pooled parameters included the area under the curve (AUC), sensitivity, specificity, and hazard ratios (HRs) to separately determine overall diagnostic and prognostic performance. Subgroup and sensitivity analyses were performed only in the event of heterogeneity. Thirty-four studies including 12 diagnostic studies and 22 prognostic studies were eligible for inclusion in this meta-analysis. We observed that miR-21, miR-26, miR-483, miR-106a, miR-150, miR-192, and miR-194 were employed for distinguishing patients with CCA from healthy controls. Pooled sensitivi...
Current Pathobiology Reports, 2014
Cholangiocytes, the cells lining bile ducts, comprise a small fraction of the total cellular component of the liver, yet perform the essential role of bile modification and transport of biliary and blood constituents. Cholangiopathies are a diverse group of biliary disorders with the cholangiocyte as the target cell; the etiopathogenesis of most cholangiopathies remains obscure. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. These small RNAs may not only be involved in the etiopathogenesis of disease, but are also showing promise as diagnostic and prognostic tools. In this brief review, we summarize recent work regarding the role of microRNAs in the etiopathogenesis of several cholangiopathies, and discuss their utility as prognostic and diagnostic tools.