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

## TL;DR

This study identifies gene expression patterns linked to vascular invasion in early-stage lung cancer, detectable in pre-surgery biopsies.

## Contribution

The study introduces a gene signature for vascular invasion detectable in limited biopsy samples, enabling preoperative risk assessment.

## Key findings

- A VI-associated gene signature was identified using bulk RNA sequencing and spatial transcriptomics.
- The predictor derived from the signature correlates with vascular invasion and recurrence in validation cohorts.
- Predictor scores from pre-surgical biopsies show promising discrimination of vascular invasion.

## Abstract

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.

Microscopic vascular invasion is an indicator of tumour recurrence in lung adenocarcinoma but is challenging to diagnose. Here, the authors use spatial transcriptomics and bulk RNA-seq to identify gene expression changes associated with vascular invasion that are detectable beyond the invasion site.