Comparison of EGFR Signaling Pathway Somatic DNA Mutations Derived From Peripheral Blood and Corresponding Tumor Tissue of Patients with Advanced Non-Small-Cell Lung Cancer Using Liquidchip Technology

Abstract

Somatic DNA mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway are known to predict responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers. Either EGFR exon 19 or 21 mutations were detected in 36 patients: 23 of whom had identical mutations in both their blood and tissue samples; whereas mutations in the remaining 13 were found only in their tumor samples. These EGFR mutations occurred at a significantly higher frequency in females, never-smokers, and in patients with adenocarcinomas (P ≤ 0.001). The EGFR exon 20 T790M mutation was detected in only one of the paired samples [100% (95% CI, 96% to 100%) agreement]. For KRAS, proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations, the overall agreements were 97% (95% CI, 90% to 99%), 98% (95% CI, 92% to 99%), and 97% (95% CI, 90% to 99%), respectively, and these were not associated with age, sex, smoking history, or histopathologic type. In conclusion, mutations detected in plasma correlated strongly with mutation profiles in each respective tumor sample, suggesting that this liquidchip platform may offer a rapid and noninvasive method for predicting tumor responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers.

Diagnostic value of circulating free DNA for the detection of EGFR mutation status in NSCLC: a systematic review and meta-analysis

“…As shown in Figure 1, after primary screening, 34 full-text articles10131415162223242526272829303132333435363738394041424344454647484950 were selected for further evaluation of eligibility. By rigorous evaluation, 20 eligible studies were identified and included in meta-analysis1314151622232425262728293031323334353637.…”

“…Circulating free DNA (cfDNA) has been proposed as an alternative approach for the detection of EGFR mutation1112. Numerous studies have investigated the diagnostic performance of cfDNA and a wide range of the concordance rates between cfDNA and tissues have been reported13141516.…”

Noninvasive Saliva-based EGFR Gene Mutation Detection in Patients with Lung Cancer

“…Limitations exist on the uncertainty of collection methods and diversity of phenotypes of CTCs in blood (8). And detecting circulating tumor DNA in plasma requires molecular methods such as polymerase chain reaction-based technology (9,10), high-performance liquid chromatography (11), and mutant-enriched liquid chips (12), which are complicated, technique dependent, and time consuming. The ideal method should be noninvasive, be readily available, need minimal or no sample preparation, and provide immediate information on EGFR mutation status, which is important for the long-term management of patients with NSCLC to enable clinicians to adjust therapeutic strategies, improving the outcome of targeted therapy.…”

Circulating tumor DNA (ctDNA) in the era of personalized cancer therapy

“…Indeed, ctDNA can be a potential source of tumor DNA alteration pursuing for the documentation of tumor-associated genetic changes in order to real-time tumor monitoring [4,53,78,79]. For NonSmall Cell Lung Cancer Research (NSCLC), numerous clinical centers have investigated the diagnostic precision of ctDNA for EGFR mutation detection [80][81][82][83]. In 2016 the U.S. Food and Drug Administration (FDA) agreed to the EGFR Mutation Test v2, a blood-based companion diagnostic for the cancer drug Tarceva (Erlotinib) [84].…”