Association of plasma DNA integrity and long fragment ALU247 in the diagnosis of epithelial ovarian cancer

Abstract

DNA Integrity index (DNA Int) and cell-free DNA (cf-DNA) represent promising biomarkers for epithelial ovarian cancer (EOC) detection. Tumor necrosis produces DNA fractions of different sizes, which contrasts apoptosis in normal tissue that releases smaller and more regular DNA fragments. Using ALU gene primers in quantitative PCR, the amplified cf-DNA is supposed to be either short fragments of 115 bp (ALU 115) or long fragments of 247 bp (ALU 247). ALU levels and DNA Int were determined in the plasma of 30 EOC patients, 30 benign cysts, and 15 healthy individuals. The mean values of DNA Int, ALU115, and ALU247 were elevated in malignant patients (0.51±0.09, 3.93 ng/ul ±1.93, 2.35 ng/ul ±1.1) respectively in comparison to healthy females (0.37±0.05; p < 0.001, 2.56 ng/ul ±0.9; p=0.027, 1.26±0.44; p< 0.01). A significant increase was shown in the mean values of DNA Int and ALU247 of EOC patients compared to those with benign cysts (0.4±0.06, p <0.001; 1.69±0.66, p =0.008) respectively. The area under the curve (AUC) for EOC versus healthy females achieved 0.913 (DNA Int), 0.696 (ALU115), and 0.809 (ALU247) with sensitivities and specificities were (86.7% and 93.3%) for DNA Int, (63.3% and 86.7%) for ALU115 and (76.7% and 86.7%) for ALU247 respectively. Furthermore, comparing patients with EOC versus those with benign cysts gave AUC of 0.834 (DNA Int), 0.564 (ALU115), and 0.681 (ALU247) with sensitivities and specificities were (80% and 80%) for DNA Int, (63.3% and 60%) for ALU115 and (60% and 80%) for ALU247 respectively. Higher DNA Int and plasma ALU247 could help in the assessment of EOC, and their measurements seem to have clinical value in diagnosis.