Molecular subtyping reveals stage-specific mutational landscape and prognostic predicting factors of stage IV NSCLC.

Abstract

e21607 Background: The mutational profile of non-small cell lung cancer (NSCLC) has been widely studied. However, the correlation between mutational profile and the prognosis of various molecular subtypes of NSCLC has not been fully investigated. Methods: We established the mutational landscape from 244 stage I-IV NSCLC patients using a 605-gene next generation sequencing panel. Molecular subtyping was performance based on the mutational status of EGFR, TP53, KRAS and STK11 genes according to reported methods. Sequencing data were analyzed with R packages and statistics analysis was performed with Graphpad PRISM 5.0 software. P ≤ 0.05 was regarded as statistically significant. Results: Differential SNV/INDEL mutation frequency across stage I-IV was found in EGFR, TP53, ATM, CDKN2A and NF1 (P < 0.05), differential CNV frequency was found in EGFR, RB1, PIK3CA, TERT, KRAS, FGFR1 and ERBB2 (P < 0.05), and differential SV frequency was found in ROS1 (P < 0.05). TMB of stage III-IV patients was higher than those of stage I (P < 0.05). TMB was higher in patients with TP53 but without EGFR mutations (P < 0.05). The association between prognosis and mutational status was further investigated in stage IV NSCLC. Patients with EGFR SNV/INDEL mutations exhibited better PFS and OS time, while patients with KRAS and/or STK11 SNV/INDEL mutations, or without mutations in EGFR, TP53, KRAS and STK11 exhibited worse PFS and OS time. However, no significant difference was observed in PFS and OS between patients with or without TP53 SNV/INDEL, EGFR CNV, ERBB2 CNV or TERT CNV variations. Further analysis showed that male or age≥62 exhibited worse OS time (P < 0.05), while smoking history, palliative surgery and palliative radiotherapy did not affect the PFS and OS time of stage IV patients. Conclusions: We found differential frequency in SNV/INDEL, CNV and SV variations across stage I-IV NSCLC. EGFR SNV/INDEL, KRAS SNV/INDEL, STK11 SNV/INDEL mutation, gender and age were found to be prognostic predicting factors for stage IV NSCLC.