1650P - The interplay of peripheral circulating free DNA and platelet-to-lymphocyte ratio in patients with differentiated thyroid cancer with/without type 2 diabetes mellitus undergoing radioiodine therapy

Background

Type 2 diabetes mellitus (T2DM) and differentiated thyroid cancer (DTC) are both endocrine system diseases. It has been found that DTC incidence in women with T2DM is constantly growing. T2DM is classified as a metabolic inflammatory disease with an altered number and function of immune cells, both innate and acquired immunity. Circulating cell-free (cf)DNA corresponds to cell-free circulating DNA fragments released in the bloodstream through inflammation, necrosis, apoptosis, or active secretion by nucleated cells such as lymphocytes. We hypothesized that cfDNA plays a key role in regulating the immune response to radioiodine (¹³¹I) therapy in patients with DTC and DTC associated with T2DM (DTC + T2DM). Our study aimed to evaluate the relationship between cfDNA and platelet-to-lymphocyte ratio (PLR) in response to ¹³¹I in DTC and DTC+T2DM patients.

Methods

Peripheral venous blood was collected in EDTA-coated vials from 56 female patients with DTC (mean age 57.3±9.1 years) and 11 with DTC+T2DM (mean age 61.6±7.8 years) before and four days after ¹³¹I therapy. Body mass index (BMI) was defined as the body mass divided by the square of the body height. cfDNA was extracted and quantified by fluorometry. PLR was measured as a systemic inflammatory biomarker.

Results

BMI and cfDNA were higher in patients with concomitant T2DM than those without (p = 0.006 and p = 0.022). cfDNA concentration was positively associated with BMI in both groups (r = 0.43 in DTC group and r = 0.60 in DTC+T2DM group). A significant modulation in cfDNA content was measured in response to ¹³¹I (reduction by 18% in the DTC group vs. increase by 7% in the DTC+T2DM group). This modulation was negatively correlated with PLR (r = − 0.41 in DTC group and r = − 0.66 in DTC+T2DM group). Analysis of PLR suggests a contribution of the host response in the altered cfDNA levels in response to ¹³¹I.

Conclusions

Our data showed that cfDNA release in response to ¹³¹I therapy depends on the patients’ immune profile. The association of cfDNA release with inflammation markers suggests its role as a predictive biomarker in DTC/DTC+T2DM patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This work was supported by a grant from the Romanian Ministry of Education and Research, CCCDI - UEFISCDI, project number PN-III-P2-2.1-PED-2019-3313, within PNCDI III.

Disclosure

All authors have declared no conflicts of interest.