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

PLoS One. 2021 Mar 12;16(3):e0247917. doi: 10.1371/journal.pone.0247917. eCollection 2021.

Abstract

Background: Early 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.

Methods: The 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.

Results: 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). 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).

Conclusion: Tumoral 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Circulating MicroRNA / blood*
  • Female
  • Humans
  • Liver Neoplasms / blood*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Liver Transplantation
  • Male
  • MicroRNAs / blood*
  • Middle Aged

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MIRN107 microRNA, human
  • MicroRNAs

Grants and funding

Work in the lab of T.L. was funded from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program through the ERC Consolidator Grant PhaseControl (Grant Agreement n° 771083). The lab of T.L. was further supported by the German Cancer Aid (Deutsche Krebshilfe 110043 and a Mildred-Scheel-Professorship), the German-Research-Foundation (SFB-TRR57/P06 and LU 1360/3-1), the Ernst-Jung-Foundation Hamburg, the IZKF (interdisciplinary centre of clinical research) Aachen and a grant from the medical faculty of the RWTH Aachen, and from a German-Research-Foundation grant (DFG, CA830-1/3) to M.C. and T.L.