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<p>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.</p>

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Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月24日

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  • 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

摘要

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.