Dataset Information

A Circulating MicroRNA Signature Capable of Assessing the Risk of Hepatocellular Carcinoma in Cirrhotic Patients.

ABSTRACT: With the availability of potent antiviral therapies, complete suppression of hepatitis B virus (HBV) replication and total eradication of hepatitis C virus (HCV) can now be achieved. Despite these advances, hepatocellular carcinoma (HCC) still develops in a substantial proportion of cirrhotic patients, suggesting that host factors remain critical. Dysregulation of miRNAs is noted in many cancers, and circulating miRNAs can be readily assayed. In this study, we aimed to develop a circulating miRNA signature to assess the risk of HCC in cirrhotic patients. We first discovered that HBV- and HCV-related cirrhotic patients had distinguishable circulating miRNA profiles. A cohort of 330 cirrhotic patients was then compared against a cohort of 42 early HCC patients with complete remission. A score comprising 5 miRNAs and a binary etiology variable was established that was capable of differentiating between these two groups (AUC = 72.5%, P < 0.001). The 330 cirrhotic patients were further stratified into high- and low-risk groups, and all patients were longitudinally followed for 752 (11-891) days. Of them, 19 patients developed HCC. The high-risk group had significantly higher cumulative HCC incidence (P = 0.038). In summary, a circulating miRNA-based score was developed that is capable of assessing HCC risks in cirrhotic patients.

SUBMITTER: Huang YH

PROVIDER: S-EPMC5428873 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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A Circulating MicroRNA Signature Capable of Assessing the Risk of Hepatocellular Carcinoma in Cirrhotic Patients.

Huang Ya-Hui YH Liang Kung-Hao KH Chien Rong-Nan RN Hu Tsung-Hui TH Lin Kwang-Huei KH Hsu Chao-Wei CW Lin Chih-Lang CL Pan Tai-Long TL Ke Po-Yuan PY Yeh Chau-Ting CT

Scientific reports 20170331 1

With the availability of potent antiviral therapies, complete suppression of hepatitis B virus (HBV) replication and total eradication of hepatitis C virus (HCV) can now be achieved. Despite these advances, hepatocellular carcinoma (HCC) still develops in a substantial proportion of cirrhotic patients, suggesting that host factors remain critical. Dysregulation of miRNAs is noted in many cancers, and circulating miRNAs can be readily assayed. In this study, we aimed to develop a circulating miRN ...[more]

PMID: 28364124

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Project description:Owing to the diagnostic dilemma, the prognosis of hepatocellular carcinoma (HCC) remains impoverished, contributing to the globally high mortality rate. Currently, HCC diagnosis depends on the combination of imaging modalities and the measurement of serum alpha-fetoprotein (AFP) levels. Nevertheless, these conventional modalities exhibit poor performance in detecting HCC at early stages. Thus, there is a pressing need to identify novel circulating biomarkers to promote diagnostic accuracy and surveillance. Circulating miRNAs are emerging as promising diagnostic tools in screening various cancers, including HCC. However, because of heterogenous and, at times, contradictory reports, the universality of miRNAs in clinical settings remains elusive. Consequently, we proposed to explore the diagnostic potential of ten miRNAs selected on a candidate-based approach in HCC diagnosis. The expression of ten candidate miRNAs (Let-7a, miR-15a, miR-26a, miR-124, miR-126, miR-155, miR-219, miR-221, miR-222, and miR-340) was investigated in serum and tissue of 66 subjects, including 33 HCC patients and 33 healthy controls (HC), by rt-PCR. Receiver operating characteristic curve (ROC) analysis was used to determine the diagnostic accuracy of the prospective serum miRNA panel. To anticipate the potential biological roles of a three-miRNA signature, the target genes were evaluated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway. The serum and tissue expression of miRNAs (Let-7a, miR-26a, miR-124, miR-155, miR-221, miR-222, and miR-340) were differentially expressed in HCC patients (p < 0.05). The ROC analysis revealed promising diagnostic performance of Let-7a (AUC = 0.801), miR-221 (AUC = 0.786), and miR-2 (AUC = 0.758) in discriminating HCC from HC. Furthermore, in a logistic regression equation, we identified a three-miRNA panel (Let-7a, miR-221, and miR-222; AUC = 0.932) with improved diagnostic efficiency in differentiating HCC from HC. Remarkably, the combination of AFP and a three-miRNA panel offered a higher accuracy of HCC diagnosis (AUC = 0.961) than AFP alone. The functional enrichment analysis demonstrated that target genes may contribute to pathways associated with HCC and cell-cycle regulation, indicating possible crosstalk of miRNAs with HCC development. To conclude, the combined classifier of a three-miRNA panel and AFP could be indispensable circulating biomarkers for HCC diagnosis. Furthermore, targeting predicted genes may provide new therapeutic clues for the treatment of aggressive HCC.

Project description:BACKGROUND: The laparoscopic approach for liver resections is still limited and controversial. Nevertheless the advantages connected with a mini-invasive approach are significant, especially in cirrhotic patients. In recent years the progress of laparoscopic procedures and the development of new and dedicated technologies have made endoscopic hepatic surgery feasible and safe. The aim of this study was to report the results of our experience in laparoscopic liver surgery for hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: From 2000 to 2003, 16 patients (10 male, 6 female; age 48-69 years; mean age 60.1 years) with HCC and associated severe but well compensated liver cirrhosis underwent laparoscopic hepatic resections at our department. Mean tumour size was 2.9 cm (range 1-3.9). Seven of these lesions were in the left liver and nine in the right lobe. Laparoscopy was performed under CO(2) pneumoperitoneum. The liver was always examined using laparoscopic ultrasound (US) to confirm the extension of the lesions and their relationships to the vasculature. The Pringle manoeuvre was not used. The transection of liver parenchyma was obtained by the use of a harmonic scalpel. The specimens were placed in a plastic bag and removed without contact to the abdominal wall. RESULTS: There was one conversion to laparotomy for inadequate exposure. In the remaining 15 patients we performed 13 non-anatomical resections, I segmentectomy and I anatomical left lobectomy. The mean operative time was 152 min (range 80-180). Mean blood loss was 280 ml and none of the patients required blood transfusions. In two patients the resection margin was <1 cm but the capsule was not infiltrated at histology. One patient died on the third postoperative day from a severe respiratory distress syndrome. Major morbidities occurred in two patients who developed moderate postoperative ascites, which resolved successfully with conservative treatment. The mean postoperative hospital stay was 8.8 days. Mean follow-up time has been 18 months, and to date no recurrences at the site of resection or port-site metastases have been observed. DISCUSSION: Limited laparoscopic liver resections in cirrhotic patients are technically feasible with a low complication rate when careful selection criteria are followed (hepatic involvement limited and located in the left or anterior right segments, tumour size smaller than 5 cm, Child-Pugh class A). This approach could be considered the best option for the treatment of small esophitic or subcapsular HCC on well compensated cirrhosis and a useful option when it is necessary to perform a left lateral anatomical resection or non-anatomical resection in well selected patients. In fact the mini-invasive approach can minimise the postoperative morbidity rate, which is still too high in this group of patients. It must be performed in highly specialised units by surgeons assisted by all requested technologies and with extensive experience in hepatobiliary and advanced laparoscopic surgery.

Dataset Information

A Circulating MicroRNA Signature Capable of Assessing the Risk of Hepatocellular Carcinoma in Cirrhotic Patients.

Publications

A Circulating MicroRNA Signature Capable of Assessing the Risk of Hepatocellular Carcinoma in Cirrhotic Patients.

Similar Datasets

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