Abstract
Detecting molecular targets in specimens from patients with lung cancer is essential for targeted therapy. Recently, we developed a highly sensitive, rapid-detection device (an immuno-wall device) that utilizes photoreactive polyvinyl alcohol immobilized with antibodies against a target protein via a streptavidin-biotin interaction. To evaluate its performance, we assayed epidermal growth factor receptor (EGFR) mutations, such as E746_A750 deletion in exon 19 or L858R substitution in exon 21, both of which are common in non-small cell lung cancer and important predictors of the treatment efficacy of EGFR tyrosine kinase inhibitors. The results showed that in 20-min assays, the devices detected as few as 1% (E746_A750 deletion) and 0.1% (L858R substitution) of mutant cells. Subsequent evaluation of detection of the mutations in surgically resected lung cancer specimens from patients with or without EGFR mutations and previously diagnosed using commercially available, clinically approved genotyping assays revealed diagnostic sensitivities of the immuno-wall device for E746_A750 deletion and L858R substitution of 85.7% and 87.5%, respectively, with specificities of 100% for both mutations. These results suggest that the immuno-wall device represents a good candidate next-generation diagnostic tool, especially for screening of EGFR mutations.
Highlights
Lung cancer is the leading cause of cancer-related mortality worldwide [1], and ~85% of lung cancers are classified as non-small cell lung cancer (NSCLC) [2]
Somatic Epidermal growth factor receptor (EGFR) mutations are detected in 10% to 16% of NSCLC patients in the United States and Europe [4] and 30% to 50% of those in Asia [5], with ~90% presenting as deletions in exon 19, most commonly the E746_A750 deletion, and an L858R substitution in exon 21
Several studies report that these mutations are associated with the sensitivity of NSCLC patients to EGFR tyrosine kinase inhibitors (TKIs) [6,7]; clinical testing for EGFR mutations has become a standard care for patients with NSCLC
Summary
Lung cancer is the leading cause of cancer-related mortality worldwide [1], and ~85% of lung cancers are classified as non-small cell lung cancer (NSCLC) [2]. Several studies report that these mutations are associated with the sensitivity of NSCLC patients to EGFR tyrosine kinase inhibitors (TKIs) [6,7]; clinical testing for EGFR mutations has become a standard care for patients with NSCLC. Other DNA-based analyses have been developed to detect EGFR mutations, including PCR-Invader [10] and peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp [11]. These methods show high sensitivity and can be used in patients with advanced NSCLC, even in those with low tumor-cell content [12]. Routine testing using these methods is often limited by the associated high costs and technical complexity [9]
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