Abstract

BackgroundCirculating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive “liquid biopsy” biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients. The aim of our study was to evaluate the possible role of cfDNA and its integrity index as a complementary tool for endometrial cancer (EC) management.MethodsAlu-quantitative real-time PCR (qPCR) analysis wasprformed on 60 serum samples from preoperative EC patients randomly recruited. Both cfDNA content and DNA integrity index were measured by qPCR-Alu115 (representing total cfDNA) and qPCR-Alu247 (corresponding to high molecular weight DNA) and correlated with clinicopathologic characteristics. Lymphovascular space invasion (LVSI) was detected by hematoxylin and eosin staining. In case of doubt, LVSI status was further evaluate by immunohistochemistry using anti-CD31 and anti-CD34 antibodies.ResultsTotal cfDNA content significantly increases in high grade EC. A significant decrease of DNA integrity index was detected in the subset of hypertensive and obese high grade EC. Serum DNA integrity was higher in samples with LVSI. The ordinal regression analysis predicted a significant correlation between decreased integrity index values and hypertension specifically in tumors presenting LVSI.ConclusionsOur study supports the utility of serum DNA integrity index as a noninvasive molecular biomarker in EC. We show that a correlation analysis between cfDNA quantitative and qualitative content and clinicopathologic features, such as blood pressure level, body mass index (BMI) and LVSI status, could represent a potential predictive signature to help stratification approaches in EC.

Highlights

  • Circulating cell-free DNA and its integrity index may represent a rapid and noninvasive “liquid biopsy” biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients

  • CfDNA content and integrity modulation in endometrial cancer (EC) CfDNA content evaluated by quantitative real-time PCR (qPCR)-Alu115 in G1 EC was very similar to that obtained from healthy specimens, whereas a significant increase of total cell-free DNA (cfDNA) content in G2 EC and G3 EC was detected (Table 2)

  • Our results showed that cfDNA integrity was significantly higher only in G3 EC as shown by the higher ratio of long to total cfDNA (Table 2)

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Summary

Introduction

Circulating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive “liquid biopsy” biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients. The aim of our study was to evaluate the possible role of cfDNA and its integrity index as a complementary tool for endometrial cancer (EC) management. Endometrial cancer (EC) is the second most common gynecological cancer and the sixth most common tumor among reproductive and postmenopausal women [1]. Recent progress in the analysis of blood samples for circulating cell-free DNA (cfDNA) provides a rapid, cost-effective, and noninvasive “liquid biopsy” tool, which gives important complementary information on. Only several years later the first experimental evidence supporting that cfDNA in cancer patients does contain tumor DNA was provided [9]

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