Multi‐omics analyses reveal distinct molecular characteristics and transformation mechanisms of stage I–III micropapillary lung adenocarcinoma

• DOI: 10.1002/path.6416
• Publication Date: 2025-03-30T19:32:39Z
• Authors: Yang Qu; Xiaoli Feng; Hanlin Chen; Fengwei Tan; Anqi Shao; Jiaohui Pang; Qi Xue; Bo Zheng; Wei Zheng; Qiuxiang Ou; Shugeng Gao; Kang Shao

Abstract The micropapillary (MIP) pattern is a high‐grade histological subtype of lung adenocarcinoma (LUAD) with poor prognosis. In this study, surgically resected tumor samples from 101 patients stage I–III MIP–LUAD (MIP ≥30%) were microdissected to separate MIP components non‐MIP components, all which underwent RNA and DNA whole‐exome sequencing (WES). genomic transcriptomic landscapes within MIP‐enriched tissues demonstrated remarkable similarities, notably marked by high epidermal growth factor receptor (EGFR) alteration frequencies. However, when compared MIP‐naïve LUAD tissues, showed higher chromosomal instability revealed 18 enriched alterations, encompassing EGFR mutations, amplifications, CDKN2A/CDKN2B deletions, linked upregulation cell proliferation pathways downregulation immune pathways. Shared mutations observed in 97.8% (91/93) paired WES data for the same suggesting common origin. recurrence‐free survival analysis identified MACF1, PCLO, ADGRV1, Fanconi Anemia pathway as negative indicators. all, we conducted an in‐depth molecular characteristics transformation mechanisms MIP–LUAD, employing microdissection techniques investigate levels substantial cohort, providing insights precision medicine aggressive cancer subtype. © 2025 Pathological Society Great Britain Ireland.