P0037 A novel method of surface-enhanced Raman scattering to detect mutant EGFR status of malignant pleural effusion

Abstract

Background Somatic mutations in the epidermal growth factor receptor (EGFR) gene are common in patients with lung adenocarcinomas and are associated with sensitivity to the small molecule tyrosine kinase inhibitors (TKIs). For 10–50% of the patients who have malignant pleural effusion (MPE), pathological diagnosis might rely exclusively on finding lung cancer cells in the MPE. Current methods based on polymerase chain reaction were used to test mutant EGFR status of MPE samples, but the accuracy of the test data is very low, resulting in many patients losing the chance of TKI treatment. Methods We synthesised a novel bioprobe, which consisted of the seaurchin-like Au nanocluster (AuNC), crystal violet, polyethylene glycol, and mutant-specific EGFR antibody. The bioprobe was used to detect the status of mutant EGFR in samples from 35 patients with lung cancer. Findings The bioprobe had excellent surface-enhanced Raman scattering (SERS) activity and recognition capability towards mutant EGFR in lung cancer cells. The enhancement factor of bioprobe reached 1.97 × 107. Characteristic SERS signal at 1617 cm−1 of CV correlated linearly with number of H1650 cells, demonstrating the minimum detection limit of 25 cells in 1 ml suspension. The quantity of bioprobes engulfed by single H1650 cells in 2 h ranged from 56 to 62. Furthermore, SERS was pre-clinically used to test mutant EGFR status in MPE samples from 35 patients with lung adenocarcinoma. Principal component analysis and support vector machine algorithms were constructed for mutant EGFR diagnostic analysis, yielding an overall accuracy of 90.7%. Interpretation SERS measurement based on sea urchin-like AuNC was an efficient method for the detection of mutant EGFR in MPE and might have potential in applications such as predicting the genotype of clinical lung cancer in the near future.