EVALUATE THE CONCENTRATION OF SERUM CFDNA AND INTEGRITY AS A NON-INVASIVE MARKER TO DISTINGUISH BETWEEN MALIGNANT AND BENIGN BREAST LESION

Abstract

under the curve (AUC) of (0.99), with ALU-247bp exhibited an area under the curve (AUC) of (1.00) and with Integrity area under the curve (AUC) is 0.89 that indicating perfect effect achieve a promising novel noninvasive approach for diagnosis and early detection of malignant breast cancer.Breast cancer is the most common cancer in the women so it important  to diagnosis and discriminate between malignant and benign breast lesion by using  biomarkers with more sensitivity and specificity than traditional biomarker Therefore, there is an urgent need for novel markers to increase  the sensitivity and specificity of diagnostic analysis. The noninvasive method to measure the concentration of circulating cell-free DNA(cfDNA) and cfDNA integrity in serum as a liquid biopsy which could replace tissue biopsy.The aim of this study was to assessed  the diagnostic values of cfDNA using it’s  concentration, ALU -247bp, ALU- 115bp and integrity in serum of patients with breast lesion as a noninvasive marker to distinguish between malignant and benign breast tumor .

In order to applicant this study , 90 women in 3 groups were collected. control group, benign breast lesions and malignant breast cancer. The serum sample of all groups were used to measure by ELISA method for determination Cancer Antigen 15.3 (CA15.3). Other part of the serum utilized for extract serum cfDNA in order to measure it’s concentration by flourometic method  using specific dye and for determined cfDNA integrity through quantitative analysis method real-time PCR , by which cfDNA integrity calculated by the ratio of the concentration of longer cfDNA fragment to shorter cfDNA fragment. The correlations determined cfDNA concentration, ALU-247bp , ALU-115bp, DNA integrity and cancer antigen (CA )15-3 between malignant breast cancer and benign breast lesion group as well as the combined relationship with traditional biomarker CA15-3.

The results showed Serum levels of cfDNA concentration, ALU-247 and cfDNA integrity significantly increased in malignant breast cancer patients compared to benign breast lesion patients (p-value =0.001 for all ) but there was less significant increase in ALU-115 (P-value =0.023). Also cfDNA concentration, ALU-247 and cfDNA integrity had the best sensitivity ( 97%, 100% and 100% respectively ) and specificity(93% ,100% and 100% respectively)  for discrimination between malignant and benign breast lesion with the value of area under the  ROC curve were (0.98 , 1 and 1 respectively ).

In conclusion  the combined ROC curves increased the ability of CA15-3 to discriminate between malignant and benign with different noninvasive biomarker. Notably, the combination of CA15-3 with cfDNA concentration, exhibited an area under the curve (AUC) of (0.99), with ALU-247bp exhibited an area under the curve (AUC) of (1.00) and with Integrity area under the curve (AUC) is 0.89 that indicating perfect effect achieve a promising novel noninvasive approach for diagnosis and early detection of malignant breast cancer.

Key Words: Malignant breast cancer, Benign breast lesion , cfDNA concentration , cfDNA integrity, ALU fragments, noninvasive biomarkers.