Whole-Exome Sequencing Reveals the Genomic Features of the Micropapillary Component in Ground-Glass Opacities

Abstract

Background: Micropapillary components are observed in a considerable proportion of ground-glass opacities (GGOs) and contribute to the poor prognosis of patients with invasive lung adenocarcinoma (LUAD). However, the underlying mutational processes related to the presence of micropapillary components remain obscure, limiting the development of clinical interventions. Methods: We collected 31 GGOs, which were separated into paired micropapillary and non-micropapillary components using microdissection. Whole-exome sequencing (WES) was performed on the GGO components, and bioinformatics analysis was conducted to reveal the genomic features of the micropapillary component in invasive LUAD. Results: The micropapillary component had more genomic variations, including tumor mutation burden, intratumoral heterogeneity, and copy number variation. We also observed the enrichment of AID/APOBEC mutation signatures and an increased activation of the RTK/Ras, Notch, and Wnt oncogenic pathways within the micropapillary component. A phylogenetic analysis further suggested that ERBB2/3/4, NCOR1/2, TP53, and ZNF469 contributed to the micropapillary component’s progression during the early invasion of LUAD, a finding that was validated in the TCGA cohort. Conclusions: Our results revealed specific mutational characteristics of the micropapillary component of invasive LUAD in an Asian population. These characteristics were associated with the formation of high-grade invasive patterns. These preliminary findings demonstrated the potential of targeting the micropapillary component in patients with early-stage LUAD.

Prognosis of early‐stage lung adenocarcinoma in young patients

“…[7][8][9] Although the clinicopathological characteristics of lung cancer in younger patients have dramatically changed over the past few decades, there is an ongoing dispute on whether their prognosis is worse than that of older patients, who may bear the brunt of their treatment strategies. [10][11][12] Administration of low-dose CT screening gained popularity, and a growing number of early-stage LUAD was detected. The idea behind this study is to ascertain whether there are any differences in survival between younger patients and older patients with invasive earlystage LUAD.…”

“…According to the data from a low‐dose computed tomography (CT) screening experiment, younger patients had early‐stage LUAD, which manifests as a nodule on CT images containing ground glass opacity (GGO) 7–9 . Although the clinicopathological characteristics of lung cancer in younger patients have dramatically changed over the past few decades, there is an ongoing dispute on whether their prognosis is worse than that of older patients, who may bear the brunt of their treatment strategies 10–12 . Administration of low‐dose CT screening gained popularity, and a growing number of early‐stage LUAD was detected.…”