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.
from sddb import Catalog
cohort = Catalog().collection("geo-gse273378")
cohort.members # the 16 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse273378")
coll.ordered_artifacts.to_dataframe() # the 16 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse273378 --dest data/Licenses: 16 NCBI GEO policy
@article{Steiner_2026,
title = {Vascular invasion-associated gene expression is detectable in pre-surgical biopsies of stage I lung adenocarcinoma},
volume = {17},
ISSN = {2041-1723},
url = {http://dx.doi.org/10.1038/s41467-026-70600-2},
DOI = {10.1038/s41467-026-70600-2},
number = {1},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
author = {Steiner, Dylan and Sultan, Lila and Sullivan, Travis and Liu, Hanqiao and Xiao, Xiaohui and LeClerc, Ashley and Melvin, Savannah and Alekseyev, Yuriy O. and Liu, Gang and Mazzilli, Sarah A. and Zhang, Jiarui and Suzuki, Kei and Rieger-Christ, Kimberly and Burks, Eric J. and Beane, Jennifer and Lenburg, Marc E.},
year = {2026},
month = Mar
}