Altered levels of circulating nuclear and mitochondrial DNA in patients with Papillary Thyroid Cancer

Abstract

Papillary thyroid cancer is the most common thyroid cancer type. However, diagnostics based on fine needle biopsy cannot make a definitive diagnosis in 25% of thyroid nodules. Additionally, approximately 70% to 80% of thyroid lobectomies performed just for diagnostic purposes are benign. Despite this, biopsy still remains the main method of evaluation of thyroid nodules. Cell-free DNA (cf-DNA) measurement could give a new diagnostic opportunities which may reduce the number of unnecessary thyroid procedures. In this study, using a qPCR, we have examined the nuclear cf-DNA and mitochondrial cf-DNA in the plasma of 32 patients. We have found that the level of nuclear cf-DNA is almost 2-fold increased (median 3 089 vs. 1 872, p = 0.022), whereas mitochondrial cf-DNA content was significantly decreased in respect to healthy controls (median 44 992 vs. 92 220, p = 0.010). The ROC curve analysis showed high specificity for nuclear cf-DNA and mitochondrial cf-DNA, which may serve as a useful tool to decrease the number of unneeded surgeries. Our study reports the first epidemiological evidence for lower mitochondrial cf-DNA content in the patient group, what suggests that apart from nuclear cf-DNA also mitochondrial cf-DNA is affected by disease development.

Analysis of Let-7 Family miRNA in Plasma as Potential Predictive Biomarkers of Diagnosis for Papillary Thyroid Cancer

“…A total of 49 patients (44 females and 5 males) with histologically confirmed PTC was enrolled. The inclusion and exclusion criteria were previously described [4]. Staging of the tumors was carried out according to the system approved by the International Union Against Cancer (UICC, 2010) and/or WHO classification.…”

“…At the same time, the number of total thyroidectomies, which are currently the recommended method of treatment, increased 2.5 times [1,2]. Almost 75% of thyroidectomies performed just for diagnostic purposes are benign [3,4]. Thus, the confirmation of innovative and more precise noninvasive biomarkers holds promise for the detection of PTC, which may decrease the number of unnecessary thyroid lobectomies and prevent the use of thyroid replacement therapy for the rest of a patient's life.…”

<p>The Blood Biomarkers of Thyroid Cancer</p>

“…39 And given the tissue-specific expression pattern and stability of miRNAs, circulating miRNAs have become ideal biomarkers for many cancers. Among the most often mentioned and proven circulating substances in PTC patients are cf-DNA, 40,41 lnc-RNAs 42 and various miRNAs. Among them, levels of miR-146, miR-221, miR-222 and let-7 were higher than those of the healthy control group [43][44][45][46][47][48] and miR-222 and miR-146b can distinguish between PTC and benign nodules.…”

An automated, high-throughput methodology optimized for quantitative cell-free mitochondrial and nuclear DNA isolation from plasma

“…Lately, ccf-nDNA has been evaluated for its utility as a reliable diagnostic and prognostic biomarker. Such investigations have demonstrated an association between increased levels of ccf-nDNA, worsened disease states, and poor clinical outcomes (8,21,22) for various conditions, including cancers (14,(23)(24)(25), chronic obstructive pulmonary disease exacerbations (21), and acute myocardial infarction (26). In addition, the discovery of cell-free fetal DNA in maternal plasma has led to the development of non-invasive blood tests to determine fetal sex, aneuploidy, RhD status, and sex-linked and somatic single-gene disorders (27)(28)(29)(30).…”