Abstract
Circulating cell-free DNA (cfDNA), which can be obtained from plasma or serum by non-invasive procedures, has showed great potential to predict treatment response and survival for cancer patients. Several studies have assessed the prognostic and predictive value of cfDNA in non-small cell lung cancer (NSCLC). However, these studies were often small and reported varying results. To address this issue, a meta-analysis was carried out. A total of 22 studies involving 2518 patients were subjected to the final analysis. Our results indicated that NSCLC patients with higher cfDNA concentration had shorter median progression-free survival (PFS) and overall survival (OS) time. In addition, high levels of cfDNA were significantly associated with poor PFS (hazard ratio or HR, 1.32; 95% CI, 1.02-1.71) and OS (HR, 1.64; 95% CI, 1.26-2.15). With respect to tumor specific mutations, we failed to reveal significant differences for PFS (HR, 1.30; 95% CI, 0.66-2.56) and OS (HR, 1.05; 95% CI, 0.49-2.25) when NSCLC patients were grouped according to KRAS genotype detected in cfDNA. However, NSCLC patients which harbored EGFR activating mutation in cfDNA had a greater chance of response to EGFR-TKIs (odds ratio or OR, 1.96; 95% CI, 1.59-2.42). No significant publication bias was detected in this study. In conclusion, cfDNA could act as a prognostic and predictive biomarker for patients with NSCLC.
Highlights
Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths in the world [1]
The total number of patients included in this study was 2518, ranging from 22 [21, 37] to 446 [29] cases per study. 12 studies evaluated the prognostic role of cell-free DNA (cfDNA) concentration in non-small cell lung cancer (NSCLC) [9, 19,20,21,22, 27,28,29,30,31,32,33]. 4 studies reported the prognostic role of KRAS genotype detected in cfDNA for NSCLC [20, 23, 25, 34]]
Another 7 studies dealt with the predictive role of epithermal growth factor receptor (EGFR) genotype presented in cfDNA for NSCLC patients who were treated with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) [16, 24, 26, 35,36,37,38]
Summary
Lung cancer is the most commonly diagnosed cancer as well as the leading cause of cancer-related deaths in the world [1]. Most NSCLC patients are diagnosed with advanced or distant stages and they are ineligible for curative surgery and often suffer a poor survival. Identifying biomarkers related to treatment response and prognosis may be helpful to improve the clinical outcome of patients with NSCLC. Circulating cell-free DNA (cfDNA), which can be isolated from the plasma or serum by non-invasive procedures, has been proposed as an attractive biomarker to estimate treatment response, detect drug resistance and predict clinical outcome for cancer patients [3,4,5,6,7]. It has been experimentally evidenced that tumor cells can release genomic DNA into the blood and circulating
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