Abstract
Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC.
Highlights
Studies have shown that DNA released from lysed or apoptotic tumor cells circulate freely in blood plasma, referred to here as circulating tumor DNA, can be isolated to aid in cancer treatment[8,9,10,11]
Most previous studies identifying mutations in Circulating tumor DNA (ctDNA) from lung cancer patients focus on advanced-stage cancers and analyze a limited number of genes[18,19], EGFR and KRAS as these are frequently mutated in lung cancers and have implications in targeted therapies[14,20]
We investigated the correlation between a series of clinicopathological variables including age, sex, smoking history, tumor histology, stage, differentiation level, ground glass opacity (GGO), vascular invasion, and visceral pleural involvement (VPI) with cell-free DNA (cfDNA) concentration in NSCLC patients (Table 2)
Summary
Studies have shown that DNA released from lysed or apoptotic tumor cells circulate freely in blood plasma, referred to here as circulating tumor DNA (ctDNA), can be isolated to aid in cancer treatment[8,9,10,11]. The next-generation sequencing Ion Personal Genome Machine (PGM) is capable of screening for mutations in multiple genes simultaneously[21], which may be useful in the clinical characterization of plasma ctDNA from lung cancer patients. The aim of this prospective study was to evaluate the feasibility of utilizing a targeted DNA sequencing approach with the Ion PGM and AmpliSeq Cancer Panel to detect mutations in 50 cancer-related genes in matched plasma ctDNA and tumor DNA (tDNA) samples from 58 early-stage NSCLC patients
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