Comparison of Circulating Plasma DNA Levels between Lung Cancer Patients and Healthy Controls

Abstract

Although the biological functions of tumor-originated cell-free DNA have not been previously clarified , such molecular characteristics as mutations , hypermethylation , and microsatellite instability have confirmed its tumor origin. Therefore , to investigate the use of plasma DNA level as a biomarker of lung cancer, we compared plasma DNA concentrations in 102 patients with lung cancer and 105 healthy individuals using quantitative PCR analyses. The median plasma DNA concentrations for the healthy and cancer groups were 10.4 and 22.6 ng/ml , respectively (P < 0.0001), and elevated plasma DNA levels were also detected in patients with either stage I or II disease. Neither smoking status nor the number of packs per year had an effect on the level of circulating cell-free DNA. Increased concentrations of circulating cell-free DNA showed the potential power to discriminate lung cancer (area under the receiver operating characteristic curve ‫؍‬ 0.86 , 95% CI ‫؍‬ 0.81 to 0.91). When subjects were classified into three groups based on their plasma DNA concentrations, subjects in the upper tertile (ie, those with the highest concentration) had a significantly increased risk of lung cancer as compared with those in the lowest tertile (adjusted odds ratio ‫؍‬ 50.6, P < 0.001). These results suggest that elevated circulating plasma DNA levels may serve as a potential diagnostic indicator and be an important risk factor for lung cancer. Lung cancer is the leading cause of cancer-related death in Korea and across the globe. Despite the development of several advanced technologies with enhanced sensitivity for detecting cancer, current screening methods for the diagnosis of lung cancer at an early stage are insufficient. Recently, circulating cell-free DNA was detected in blood fractions from patients with cancer. Since then, efforts have been made to use circulating cell-free DNA as a diagnostic or prognostic factor for lung cancer.

Circulating Cell-Free DNA in Plasma of Never Smokers with Advanced Lung Adenocarcinoma Receiving Gefitinib or Standard Chemotherapy as First-Line Therapy

“…Thus, circulating plasma cell-free DNA (CFDNA) may, in theory, represent tumor burden or tumor biologic aggressiveness, regardless of the releasing mechanisms. A series of studies has shown that lung cancer patients have higher levels of CFDNA in the blood compared with healthy controls (7)(8)(9). However, the prognostic or predictive value of circulating plasma CFDNA for the treatment outcomes and survival of lung cancer patients remains controversial (9)(10)(11)(12)(13)(14)(15).…”

Key epigenetic changes associated with lung cancer development

“…For example, lung cancer cases have significantly more serum-derived DNA than controls (p < 0.0001). 25 In non-small cell lung cancer patients, Esteller et al showed that when a patient's tumor was positive for methylation (at one of four investigated genes) 73% of the time methylated DNA was also detectable in the serum. 26 Other work in lung cancer has been similar: in 2002, An et al showed that 88% of patients (n = 64/73) with CDKN2A methylation in tumors also had methylation in serum-derived DNA.…”

Rational Design of Materials Interface for Efficient Capture of Circulating Tumor Cells

“…Similarly, in a recent study, CTCs captured on the aptamer‐functionalized SiNWs substrates were distinguished from non‐specifically trapped WBCs by using a three‐color immunological method based on FITC‐labeled anti‐EpCAM, Cy5‐labeled anti‐CD45, and DAPI nuclear staining 117. Most CTCs molecular identification methods use DNA testing techniques such as polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to analyze the specific DNA or mRNA of CTCs enriched 117, 118. PCR‐based analysis technique are the most widely used molecular method for CTCs detection and identification.…”

“…For example, in size filtration‐based microfluidic system with microcavity arrays, two fluorescent immunological probes of FITC‐labelled anti‐CD45 antibody and PE‐labelled anti‐EpCAM antibody were employed to detect and identify CTCs captured on the microcavity arrays 59. Similarly, in a recent study, CTCs captured on the aptamer‐functionalized SiNWs substrates were distinguished from non‐specifically trapped WBCs by using a three‐color immunological method based on FITC‐labeled anti‐EpCAM, Cy5‐labeled anti‐CD45, and DAPI nuclear staining 117. Most CTCs molecular identification methods use DNA testing techniques such as polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to analyze the specific DNA or mRNA of CTCs enriched 117, 118.…”