Genetic characteristics of lung adenocarcinoma with ground-glass opacity component

Background: Increasing evidence suggests that ground-glass opacity featured lung adenocarcinoma (GGO-LUAD) and pure solid-LUAD have significantly different tumor biological behaviors; the former is usually indolent. Genetic variations fundamentally contribute to this distinct tumor behaviors. This study aims to investigate and compare the gene mutations using next-generation sequencing (NGS) technology in these two subtypes of LUAD. Methods: The clinical data and gene testing results of 46 patients suffering from LUAD with a histologically invasive subtype ≤3 cm and operated in the Thoracic Surgery Department of Beijing Tsinghua Changgung Hospital from May 2019 to December 2022 were retrospectively analyzed; a case-control study was performed to compare the pathological and genetic differences between LUAD with a GGO component and pure solid-LUAD. Results: Notable differences existed in vascular invasion, tumor spread through air spaces (STAS) and high-risk histological subtypes (micropapillary or solid subtypes) between the two types of LUAD with similar histologically invasive size. No significant difference was found in the mutation frequency of EGFR and KRAS. However, gene mutations were more prevalent in the cell cycle and TP53 signaling pathway for solid-LUAD. A significant difference was found in the mutation frequency of the tumor suppressor genes TP53 and CDKN2A between the two types. Conclusions: The wild-type TP53 and CDKN2A genes could potentially be used as molecular indicators for indolent LUAD characterized by GGO-featured.