Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma
- Dylan Steiner
- Lila Sultan
- Travis Sullivan
- Hanqiao Liu
- Xiaohui Xiao
- Ashley LeClerc
- Savannah Melvin
- Yuriy O. Alekseyev
- Gang Liu
- Sarah A. Mazzilli
- Jiarui Zhang
- Kei Suzuki
- Kimberly Rieger-Christ
- Eric J. Burks
- Jennifer Beane
- Marc E. Lenburg
2026-03-24
Microscopic vascular invasion (VI) predicts recurrence and benefit from lobectomy in stage I lung adenocarcinoma (LUAD) but cannot be accurately predicted before surgery. Thus, biomarkers that identify this aggressive tumor subset are needed. Here, we show that VI in stage I LUAD is associated with reproducible gene expression programs detectable beyond the invasive focus. Using bulk RNA sequencing of 162 resected tumors and spatial transcriptomics in a subset, we identify and characterize a VI-associated gene signature. A predictor derived from this signature is associated with VI and recurrence in an independent validation cohort and is robust to intra-tumor heterogeneity in multiregional sampling data. In a cohort of pre-surgical biopsies, predictor scores correlate with matched resections and show promising discrimination of VI. These findings indicate that VI-associated transcriptional changes extend across the tumor and are detectable in limited biopsy material, supporting further validation for preoperative risk stratification in stage I LUAD.