Next-Generation Sequencing in Early-Stage Multiple Primary Lung Cancer: The Prognostic Significance of Genomic Accumulation Status and BCL2L11 del

Abstract

Objective: This study aimed to define the genomic features of tumors and to delineate the potential mutational pattern underlying the prognosis of patients using large-panel next-generation sequencing (NGS) assays. Methods: A total of 53 patients were enrolled, with a total of 130 malignant tumors. Clinical variables were collected, and the NGS sequencing of a large panel of 116 tumor-associated genes was performed. According to the gene mutation series and the number of mutation sites, the patients were divided into a series of groups. We investigated the relationship between the clinical–genetic features and the prognosis of MPLCs. Results: The patients exceeding the IA stage were associated with a significantly shorter DFS than those in the IA stage (mean time: 27.5 vs. 50.6 months, p = 0.044), and BCL2L11^del subsets were associated with a significantly worse DFS (31.9 vs. 50.2 months, p= 0.047). In the subgroups, the patients with a single gene mutation series with multiple gene mutation sites had a shorter DFS than those with a single mutation site (37.6 vs. 53.9 months, p = 0.047); and those with four gene series with over four mutation sites displayed a longer DFS than those with four sites (25.7 vs. 58 months, p = 0.034). In a Cox Multivariate analysis, exceeding the IA stage and a BCL2L11^del mutation were considered unfavorable independent prognostic factors (HR = 5.102, 95%CI: 1.526 to 17.054; p = 0.008, and HR = 6.010, 95%CI: 1.636 to 22.079; p = 0.007, respectively). A lower gene mutation series (≤2) was an independent factor for a longer DFS (HR = 0.276, 95%CI: 0.086 to 0.882; p = 0.03). Conclusions: The prognosis of patients with early-stage MPLC may potentially be related to the accumulation status of gene mutation series and sites; their driving powers may offset each other. Taken together, the application of genomic profiling may prove to be useful for subdividing and precisely managing patients with MPLC.