Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer

Abstract

BackgroundNon-small cell lung cancer (NSCLC) is leading cause of cancer related death and the survival rate for patients with NSCLC remain poor so early diagnosis of NSCLC represents the best opportunity for cure. Cell-free DNA (cf-DNA) is extracellular nucleic acids found in cell-free plasma/serum of humans, given the recent approval of a liquid biopsy in lung cancer, the use of circulating tumor DNA as a novel non-invasive diagnostic and prognostic biomarker is promising.ObjectivesStudying whether the concentrations of circulating Cell Free DNA in serum can be used as a diagnostic and prognostic biomarker for NSCLC patients.MethodThis study was carried out on 140 subjects included 60 patients with non small cell lung cancer,40 patients with Chronic Obstructive Pulmonary Disease (COPD) and 40 healthy controls. Quantitative analysis of serum circulating cf-DNA was done b y AlU-based quantitative real time PCR. Serum level of CEA was measured by ELISA.ResultsNSCLC patients demonstrated significantly higher values of each of ALU 215, ALU 247, and DNA integrity than both COPD patients and controls. On ROC curve analysis, the total accuracy of ALU 247, ALU 115, DNA integrity (92.1%, 83.6%, 56.4%) at cutoff points (325, 565 & 0.48) respectively. On combining both DNA integrity and CEA, improved sensitivity to 93.3% was noted. For NSCLC patients, ALU 115 & ALU 247 increased significantly with more advanced stage and highest level was noticed in metastatic patients. Regarding survival there was better overall survival among patients with low DNA integrity.ConclusionSerum cf-DNA concentrations and integrity index may be valuable tool in early diagnosis of NSCLC and prediction of prognosis of those patients.

Limited Utility of Circulating Cell-Free DNA Integrity as a Diagnostic Tool for Differentiating Between Malignant and Benign Thyroid Nodules With Indeterminate Cytology (Bethesda Category III)

“…Even though we observed a significant difference in the plasma concentration of ALU115 and ALU247 between benign and malignant thyroid nodules, its clinical utility is limited due to a significant overlap. Although various studies have reported an increase in DNA concentration in cancer patients (22)(23)(24)(25)(26), numerous studies have indicated the limited utility of cfDNA concentration as a biomarker, owing to the wide variations in cfDNA level among the population (11). Moreover, we observed that the concentration difference could be attributed to the size of the lesions since patients with benign lesions were characterized by the larger tumor size, which was associated with the higher ALU115 and ALU247 levels.…”

Liquid Biopsy is Instrumental for 3PM Dimensional Solutions in Cancer Management

“…The concentration of tumor-associated biomarkers released into the bloodstream might contribute to early detection of cancer and more favorable prediction of patients’ prognosis [ 84 ]. The emerging role of blood-based liquid biopsy in the management of cancer patients [ 85 ] in terms of predictive, personalized, and preventive medicine is based on the analysis of CTCs, genetic and epigenetic changes at the ctDNA level (such as mutations or DNA methylation) [ 86 , 87 , 88 , 89 , 90 ], EVs and their content derived from the original cancer cell [ 91 , 92 , 93 ], and protein-based markers [ 94 , 95 , 96 , 97 ] or their combinations [ 98 ] ( Figure 2 ). Therefore, the detection of tumor biomarkers freely circulating in blood through liquid biopsy is associated with new opportunities for early diagnosis and therapy of cancer [ 99 , 100 ].…”

“…Circulating tumor cell-free DNA (ctDNA) is defined as tumor-derived extracellular nucleic acid in cell-free plasma or serum that is currently gaining a promising potential as a novel diagnostic and prognostic tool in cancer management [ 86 , 93 , 101 ]. Peripheral blood is the most common source of ctDNA but it could be detected also in other biofluids such as saliva, urine, ascites, and PE [ 102 ].…”

“…The concentrations of circulating ctDNA in serum represent a valuable tool in early diagnosis and prediction of prognosis of non-small cell lung cancer (NSCLC) patients [ 86 ]. An analysis of circulating cell-free DNA is a useful alternative for the selection of advanced NSCLC patients carrying activating mutations of EGFR who might benefit from the rechallenge with the first-generation tyrosine kinase inhibitor gefitinib [ 87 ].…”

“…Therefore, the clinical utilization of non-invasive methods such as liquid biopsy represent a promising approach for early cancer detection and improvements of survival rates of patients with various cancer types [ 197 ]. As discussed above, an evaluation of biomarkers from various types of liquid biopsy is associated with high applicability in the framework of early detection of various cancer types, such as lung [ 86 , 118 , 177 ], breast [ 112 , 151 ], bladder [ 120 ], gastric [ 95 ], cervical [ 98 ], endometrial [ 192 ], or ovarian cancer [ 35 , 121 ] ( Figure 3 ). The application of liquid biopsy in cancer screening and early diagnosis represent the most promising aspects of its clinical utilization [ 46 ].…”