| Abstract [eng] |
Mutation Analysis in Liquid Biopsy from Non-Small Cell Lung Cancer Patients Lung cancer (LC) is one of the most common cancer worldwide with lowest survival rate among other cancer types. Routine disease monitoring using liquid biopsy could allow to detect disease progression earlier and consequently lower the death rate. PV is known for 11 most common EGFR, ALK, BRAF, ERBB2, KRAS, MAP2K1, MET, NRAS, PIK3CA, ROS1 and TP53 somatic mutations. Changes in these genes by mutation, mutation frequency during disease progression could be used as molecular markers to detect LC formation, disease progression. The study was focused on analysing 11 gene attributed to LC mutations, mutation count and frequency in non-small cell LC subtypes lung adenocarcinoma (LA), squamous cell lung cancer (SCLC) and pleomorphic adenocarcinoma (PA) in blood plasma (BP) and pleural effusion (PE) samples. Analysis by next generation sequencing was conducted in before progression 31 BP and 8 PE samples and in 23 serial KP samples. Out of all analysed before progression most common were KRAS 24/48 (50.0%) and PIK3CA 13/48 (27.1%) mutations. Mutations were cooccurring in 3/8 (37.8%) paired BP and PE samples. After mutation count and read count with mutation comparison according to stage overall mutation count was highest in stage IV (RSP=1.00; p=0.083) and read count with mutations was 2-fold higher in IV vs III (289.9 vs 152.5; p=0.234). Correlation with age and differences according to sex were not detected (RSP=-0.036; p=0.0846 and p= 0.351). In serial samples before progression mutation frequency was lower in 5/11 (45.5%) while in 6/11 (54.5%) patients mutations were not found. After disease progression in 6/7 (85.7%) mutation frequency varied while in 2/7 (28.6%) new mutations were found. Mutation count, frequency differences in liquid biopsy samples could be due to non-small cell LC progression and these differences could be used as prognostic biomarker. |
