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.

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.

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