Novel Technology Enables Detection of Early-Stage Cancer

Non-small-cell lung carcinoma (NSCLC) is often fatal because most cases are not diagnosed until they are so advanced that surgical intervention is no longer possible. To improve outcomes a blood test has been developed to detect lung cancer earlier in the disease.

Despite advances in chemotherapy, five-year survival for patients diagnosed with unresectable or a malignancy that cannot be removed completely through surgery, NSCLC is less than 10%. The ability to diagnose NSCLC in stages 1 and 2, when surgical resection and potential cure are still possible, could significantly reduce the mortality from NSCLC worldwide.

Scientists at the University of California Los Angeles (Los Angeles, CA, USA) and their colleagues in Taiwan collected plasma samples from 248 patients with radiographically determined pulmonary nodules from December 2014 through March 2016. Of those, 44 were diagnosed with Stage I or Stage II NSCLC; 23 with biopsy-proven benign pulmonary nodules and 21 with Stage I or Stage II adenocarcinoma. Samples were analyzed for the EGFR mutations using the electric field–induced release and measurement (EFIRM) platform.

The team investigated the ability of an EFIRM LB (eLB) assay to detect p.L858R and exon19 del EGFR variants in direct plasma samples from patients with early-stage NSCLC and correlated the results with those from the biopsy of the tumor itself. eLB is an open platform signal amplification technology based on a microtiter plate of 96 gold electrodes obtained from EZLife Bio (Guangzhou, China). Initially, capture probes (100 nmol/L) are copolymerized with conduction gel and pyrrole onto the gold electrodes so that each well contains a single capture probe specific to a single variant. In this assay, either of two well-characterized tyrosine kinase inhibitor–sensitizing EGFR variants, the exon19 del or p.L858R point mutation, were measured.

EFIRM was able to detect the p.L858R mutation in 11 of 12 samples and the Exon 19del mutation in seven of nine samples, resulting in greater than 90% sensitivity and 80% specificity. Visual inspection demonstrates excellent discrimination between the individuals with tumors harboring the exon19 del variant and both the patients with benign nodule (wild type) and those with the p.L858R variant. Results with the exon19 del capture probe demonstrated that none of the patients with benign nodules or those with the p.L858R mutation had electrical current values of <−230 nA, whereas all but one sample from patients with biopsy-proven exon19 del had values of <−240 nA. The 0.978 area under the AUC curve reinforces this observation.

Wu-Chou Su, MD, a co-corresponding author of the study, said, “Currently, the clinical sensitivity of EFIRM to detect patients with NSCLC is limited by the percentage of tumors containing either or both of the two variants, which is estimated at 27% of NSCLC tumors. We are presently developing a 10-variant panel that contains detecting mutations expressed in 50% of all lung malignancies.” The study was published on October 8, 2018, in The Journal of Molecular Diagnostics.

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University of California Los Angeles
EZLife Bio