Fig. 3. Molecular events associated with the stepwise progression of LUAD.

In a series of processes from precancerous lesions to AIS, MIA, and invasive adenocarcinoma, epigenetic alterations such as RUNX3 inactivation occur first (oncogenic initiation), and then driver mutations in genes such as EGFR and K-RAS are activated (oncogenic activation). Finally, the development of TP53 mutation causes invasion and metastasis (oncogenic progression).