Serum levels of circulating microRNA-107 are elevated in patients with early-stage HCC.

Sven H Loosen,Tom F Ulmer,Frank Tacke,Tom Luedde,Jennis Kandler,Sanchary Roy,Linda Hammerich,Markus S Jördens,Christoph Roderburg,Mihael Vucur,Ulf P Neumann,Raphael Mohr,Mirco Castoldi,Matias A Avila

doi:10.1371/journal.pone.0247917

Abstract

BackgroundEarly detection of hepatocellular carcinoma (HCC), the most common primary liver malignancy, is crucial to offer patients a potentially curative treatment strategy such as surgical resection or liver transplantation (LT). However, easily accessible biomarkers facilitating an early diagnosis of HCC as well as a reliable risk prediction are currently missing. The microRNA(miR)-107 has recently been described as a driver of HCC in both murine and human HCC but data on circulating miR-107 in HCC patients are scarce. In the present study, we evaluated a potential diagnostic and/or prognostic role of circulating miR-107 in patients undergoing tumor resection or LT for early-stage HCC.MethodsThe Kmplot bioinformatic tool was used to query publicly available databases (including TCGA, GEO and EGA) in order to analyse the prognostic value of tumoral miR-107 expression in HCC patients (n = 372). Serum levels of miR-107 were measured by qPCR in n = 45 HCC patients undergoing surgical tumor resection (n = 37) or LT (n = 8) as well as n = 18 healthy control samples. Results were correlated with clinical data.ResultsA high tumoral expression of miR-107 was associated with a significantly better overall survival compared to patients with low miR-107 expression levels (HR 0.69, 95% CI 0.48–0.99, p = 0.041). In addition, serum levels of miR-107 were significantly higher in HCC patients when compared to healthy controls. However, miR-107 serum levels in HCC patients were independent of different disease etiology, tumor stage or tumor grading. HCC patients with baseline miR-107 expression levels above a calculated ideal prognostic cut-off value (9.82) showed a clear trend towards an impaired overall survival (p = 0.119).ConclusionTumoral miR-107 expression levels are a potential prognostic marker in early stage HCC. Furthermore, we describe a potential role of circulating miR-107 levels as a diagnostic biomarker in patients with early-stage HCC.

Highlights

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and has risen to become the fifth most common cancer worldwide
A high tumoral expression of miR-107 was associated with a significantly better overall survival compared to patients with low miR-107 expression levels (HR 0.69, 95% CI 0.48–0.99, p = 0.041)
Tumoral miR-107 expression levels are a prognostic marker for overall survival in HCC patients

Summary

Introduction

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and has risen to become the fifth most common cancer worldwide. Surgical tumor resection and liver transplantation (LT) represent two standard therapies that can potentially provide cure for HCC patients at early stage (Barcelona Clinic Liver Cancer [BCLC] 0 or A [2]). In many patients, it often remains unclear whether they will benefit from surgery or not In this context, different prognostic algorithms (including imaging modalities, laboratory markers and the ECOG performance status) have been proposed to discriminate between patients who benefit from liver resection or LT and should be allocated to a surgical approach and those who do not [5]. Detection of hepatocellular carcinoma (HCC), the most common primary liver malignancy, is crucial to offer patients a potentially curative treatment strategy such as surgical resection or liver transplantation (LT). We evaluated a potential diagnostic and/or prognostic role of circulating miR-107 in patients undergoing tumor resection or LT for early-stage HCC.

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Results

Conclusion