Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

Loosen, Sven H.; Wirtz, Theresa H.; Roy, Sanchari; Vucur, Mihael; Castoldi, Mirco; Schneider, Anne T.; Koppe, Christiane; Ulmer, Tom Florian; Roeth, Anjali A.; Bednarsch, Jan; Alizai, Patrick H.; Paffenholz, Pia; Demir, Münevver; Tacke, Frank; Neumann, Ulf; Roderburg, Christoph; Luedde, Tom

doi:10.1371/journal.pone.0239386

Cited by 14 publications

(13 citation statements)

References 29 publications

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“…Interestingly, both groups demonstrated a comparable OS ( Fig 4A ). As the median might not be the optimal cut-off for the discrimination between patients with a favorable/unfavorable prognosis, we aimed at establishing a statistically optimal prognostic cut-off value by using a univariate binary cox proportional hazard model and testing for the minimum p-value as recently described [ 11 ]. By applying this cut-off value (9.82 relative units), we observed a strong trend towards an impaired survival in patients with miR-107 levels > 9.82, however the difference failed statistical significance (p = 0.119).…”

Section: Resultsmentioning

confidence: 99%

“…Based on the tumoral expression data suggesting a crucial role of miR-107 in HCC, we next aimed at measuring levels of circulating miR-107 in patients with early-stage HCC, representing the patient group being at highest need for the development of markers suitable for early detection of cancer. Between 2011 and 2017, we enclosed a total of n = 45 patients who presented with HCC and were allocated to either tumor resection (n = 37) or liver transplantation (LT, n = 8) [11]. The median age of the study population was 66 years (range: 42-82 years https://doi.org/10.1371/journal.pone.0247917.g001…”

Section: Baseline Characteristics Of Hcc Cohortmentioning

confidence: 99%

“…In line, we have recently demonstrated that miR-193a-5p in down regulated in both murine and human HCC, leading to a more aggressive course of disease [ 10 ]. Interestingly, the intratumoral down-regulation of miR-193a-5p was associated with elevated serum levels of this miRNAs in HCC patients [ 11 ]. Alongside miR-193a-5p, our array-based analysis in mice revealed a down-regulation of miR-107 (personal communication with Dr. Castoldi), which has been shown to be involved in the regulation of glucose homeostasis and insulin sensitivity in the liver [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Baseline Characteristics Of Hcc Cohortmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Loosen et al identified miRNA-193a-5p as a potential biomarker in the context of HCC as circulating relative miRNA-193a-5p levels were significantly elevated and predictive for patients’ outcome after tumor resection [ 61 ]. In line with this, Liu et al described a significant difference in miRNA-193-a-5p levels in serum of HCC patients compared to non-HCC patients, without any difference among patients with liver cirrhosis, chronic hepatitis B, and healthy controls [ 119 ].…”

Section: Specific Mirnas Involved In Hepatocarcinogenesismentioning

confidence: 99%

From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis

Mohr

Özdirik

Lambrecht

et al. 2021

IJMS

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In almost all cases, hepatocellular carcinoma (HCC) develops as the endpoint of a sequence that starts with chronic liver injury, progresses to liver cirrhosis, and finally, over years and decades, results in liver cancer. Recently, the role of non-coding RNA such as microRNA (miRNA) has been demonstrated in the context of chronic liver diseases and HCC. Moreover, data from a phase II trial suggested a potential role of microRNAs as therapeutics in hepatitis-C-virus infection, representing a significant risk factor for development of liver cirrhosis and HCC. Despite progress in the clinical management of chronic liver diseases, pharmacological treatment options for patients with liver cirrhosis and/or advanced HCC are still limited. With their potential to regulate whole networks of genes, miRNA might be used as novel therapeutics in these patients but could also serve as biomarkers for improved patient stratification. In this review, we discuss available data on the role of miRNA in the transition from liver cirrhosis to HCC. We highlight opportunities for clinical translation and discuss open issues applicable to future developments.

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“…Low levels of miR-1, miR-122, miR-26a, miR-29a and miR-223-3p were associated with lower survival [ 50 , 51 , 52 , 56 ]. Patients with high levels of miR-155, miR-96 and miR-193-5p had lower survival rates [ 53 , 55 ]. A recent study reported whole miRNome profiling in 116 HCC patients [ 54 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Liquid Biopsy in Hepatocellular Carcinoma Prognostication

Labgaa

Villanueva

Dormond

et al. 2021

Cancers

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Showing a steadily increasing cancer-related mortality, the epidemiological evolution of hepatocellular carcinoma (HCC) is concerning. Numerous strategies have attempted to prognosticate HCC but their performance is modest; this is partially due to the heterogeneous biology of this cancer. Current clinical guidelines endorse classifications and scores that use clinical variables, such as the Barcelona Clinic Liver Cancer (BCLC) classification. These algorithms are unlikely to fully recapitulate the genomic complexity of HCC. Integrating molecular readouts on a patient-basis, following a precision-medicine perspective, might be an option to refine prognostic systems. The limited access to HCC tissue samples is an important limitation to these approaches but it could be partially circumvented by using liquid biopsy. This concept consists of the molecular analysis of products derived from a solid tumor and released into biological fluids, mostly into the bloodstream. It offers an easy and minimally-invasive access to DNA, RNA, extracellular vesicles and cells that can be analyzed with next-generation sequencing (NGS) technologies. This review aims to investigate the potential contributions of liquid biopsy in HCC prognostication. The results identified prognostic values for each of the components of liquid biopsy, suggesting that this technology may help refine HCC prognostication.

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Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

Cited by 14 publications

References 29 publications

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

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

From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis

The Role of Liquid Biopsy in Hepatocellular Carcinoma Prognostication

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