GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300827/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300827GEOGSEfalseSpatial transcriptome of pre-invasive lung adenocarcinomaWe observed distinct mutational patterns across stages: EGFR mutations increased with pathological stages, while non-V600E BRAF mutations were enriched in AAH and AIS, suggesting pre-invasive lesions harboring different drivers follow distinct evolutionary paths. Based on these differences, we derived 23-gene and 59-gene signatures that stratified pre-invasive lesions into aggressive and non-aggressive groups. The aggressive signature was associated with worse prognosis supported by five stage-I LUAD cohorts. Two aggressive signature genes, LPGAT1 and XPR1, were functionally validated to promote LUAD cell invasion. Compared to non-aggressive lesions, aggressive lesions exhibited higher tumor mutation burden, enrichment of proliferative and EMT-related pathways, and evidence of immune-stromal remodeling.2026/06/30GSE300827GSM9069319GSM9069308GSM9069309GSM9069322GSM9069311GSM9069323GSM9069312GSM9069313GSM9069314GSM9069315GSM9069304GSM9069305GSM9069316GSM9069317GSM9069306GSM9069318GSM9069307GSM9069320GSM9069321GSM906931024676300827Homo sapiens