Circulating cf-miRNA as a more appropriate surrogate liquid biopsy marker than cfDNA for ovarian cancer

Abstract

Ovarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years. Liquid biopsy markers have great potential to improve current diagnostic and prognostic methods. Here, we compared miRNAs and DNA methylation in matched plasma, whole blood and tissues as a surrogate marker for OC. We found that while both cfDNA and cf-miRNAs levels were upregulated in OC compared to patients with benign lesions or healthy controls, only cf-miRNA levels were an independent prognosticator of survival. Following on our previous work, we found members of the miR-200 family, miR-200c and miR-141 to be upregulated in both plasma and matched tissues of OC patients which correlated with adverse clinical features. We could also show that the upregulation of miR-200c and -141 correlated with promoter DNA hypomethylation in tissues, but not in plasma or matched whole blood samples. As cf-miRNAs are more easily obtained and very stable in blood, we conclude that they might serve as a more appropriate surrogate liquid biopsy marker than cfDNA for OC.

The Circulating Biomarkers League: Combining miRNAs with Cell-Free DNAs and Proteins

“…The superiority of c-miRNAs over cfDNA was underscored in a recent study by Gahlawat et al [ 144 ], which highlighted the advantages of c-miRNAs as biomarkers in ovarian cancer (OC) research and identified miR-200c as a potential biomarker. Their study compared miRNAs and DNA methylation across plasma, whole blood, and tissues to evaluate their efficacy as surrogate markers for OC.…”

“…Examples of these applications are summarized in Table 3. Importantly, c-miRNAs offer several advantages over cfDNA, underlining their potential as superior biomarkers [144,145]. Firstly, c-miRNAs demonstrate remarkable stability and robustness in various biological fluids, including blood, urine, and saliva.…”

Liquid biopsy: from concept to clinical application

“…Gahlawat et al reported that circulating cell-free miRNA can be more easily obtained as a very stable biomarker population in blood, thus it might serve as a more appropriate surrogate liquid biopsy marker than cfDNA for ovarian cancer 11 .…”

Analytical platform to validate microRNA biomarkers for cancer or disease with practically 100% sensitivity and specificity

“…No single diagnostic test is available for pancreatic cancer. Serum levels of the antigen CA 19-9 higher than 37 U/mL are exploited for the diagnosis of pancreatic cancer in symptomatic patients, but they are not useful as screening markers in asymptomatic individuals illustrated that miRNAs are stable in the blood, which renders them viable biomarkers [20], and empowered more than 150,000 peer-reviewed studies worldwide [21][22][23][24][25][26][27][28][29][30]. Several studies have investigated the expression of miR-375 and miR-141 in multiple cancer indications, and many have confirmed that these miRNAs are overexpressed in the serum of cancer patients compared with healthy controls [20,23,26].…”

“…miRNAs are abundant in most eukaryotes, and approximately 2500 known miRNAs are common to all humans [18,19]. In 2008, Mitchell et al illustrated that miRNAs are stable in the blood, which renders them viable biomarkers [20], and empowered more than 150,000 peer-reviewed studies worldwide [21][22][23][24][25][26][27][28][29][30]. Several studies have investigated the expression of miR-375 and miR-141 in multiple cancer indications, and many have confirmed that these miRNAs are overexpressed in the serum of cancer patients compared with healthy controls [20,23,26].…”