Furong Chen ¹ Jiangtao Li ¹ Lei Li ² Lunbing Tong ³ Gang Wang ⁴ Xue-lin Zou ^3*

• ¹ Department of Oncology, The First People’s Hospital of Shuangliu District, Chengdu, Chengdu, China
• ² Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, Department of State Key Laboratory of Respiratory Health and Multimobidity, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
• ³ Department of Respiratory Medicine, Chengdu Seventh People's Hospital, Chengdu, Sichuan Province, China
• ⁴ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, Department of State Key Laboratory of Respiratory Health and Multimobidity, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

The detection rate of ground glass nodules (GGNs) has increased in recent years because of their malignant potential but relatively indolent biological behavior; thus, correct GGN recognition and management has become a research focus. Many scholars have explored the underlying mechanism of the indolent progression of GGNs from several perspectives, such as pathological type, genomic mutational characteristics, and immune microenvironment. GGNs have different major mutated genes at different stages of development; EGFR mutation is the most common mutation in GGNs, and p53 mutation is the most abundant mutation in the invasive stage of GGNs. Pure GGNs have fewer genomic alterations and a simpler genomic profile and exhibit a gradually evolving genomic mutation profile as the pathology progresses. Compared to advanced lung adenocarcinoma, GGN lung adenocarcinoma has a higher immune cell percentage, is under immune surveillance, and has less immune escape. However, as the pathological progression and solid component increase, negative immune regulation and immune escape increase gradually, and a suppressive immune environment is established gradually. Currently, regular computer tomography monitoring and surgery are the main treatment strategies for persistent GGNs. Stereotactic body radiotherapy and radiofrequency ablation are two local therapeutic alternatives, and systemic therapy has been progressively studied for lung cancer with GGNs. In the present review, we discuss the characterization of the multidimensional molecular evolution of GGNs that could facilitate more precise differentiation of such highly heterogeneous lesions, laying a foundation for the development of more effective individualized treatment plans.