Circulating cell free DNA integrity index as a Biomarker for response to chemotherapy in patients with metastatic colorectal carcinoma / Nancy Samir Eskander ; Supervised Lamia Ali Mansour , Amaal Abdo Abdelaal , Doaa Mohamed Abdo

Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Background: Early evaluation of response to chemotherapy in mCRC may help personalize treatment strategies, identify patients who are likely to benefit from intense chemotherapy regimens and spare predicted non-responders from unnecessary side effects. Objective: Assessing plasma cfDNA integrity index as a biomarker for response prediction and early response evaluation in mCRC patients receiving chemotherapy, compared to CEA and CA19-9, to be used as an additional tool to CT. Subjects and methods: CEA, CA19-9, cfDNA concentration and cfDNA integrity index (ALU 247/115) measurements were conducted on 86 subjects divided into 43 mCRC patients and 43 healthy volunteers. Plasma cfDNA integrity index was calculated as the ratio of long to short DNA fragments (ALU 247/115) amplified and detected by real-time PCR. Serum CEA and CA19-9 were measured by chemiluminescent immunometric assay Results: cfDNA integrity index was statistically significant before chemotherapy between responders and non-responders at baseline (p=0.03). It was found that at cut off 0.608, sensitivity was 73.7%, specificity was 66.7% and diagnostic accuracy=69.77%. The markers that showed statistical significant difference between responders and non-responders after chemotherapy were CEA % change (p=0.035), CA 19-9 (p=0.024), DNA integrity index (p=0.035) and DNA integrity index % change (p<0.001). Among these markers, cfDNA integrity index % change had the best sensitivity (84.2%), specificity (95.2%) and diagnostic accuracy (90.7%) at cut off -17.827%

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