Multi-region spatial transcriptome analysis reveals cellular networks and pathways associated with hepatocellular carcinoma recurrence after surgical resection
Hepatocellular carcinoma (HCC) exhibits diverse aetiologies and molecular heterogeneities, with a median 5-year overall survival (OS) of less than 70% due to late diagnosis and high recurrence rates post-curative ablation or surgery. This study investigated the complex tumor microenvironment (TME) in HCC, emphasizing the interactions between various cell types and their role in disease recurrence. Using samples from the PLANet 1.0 cohort (NCT03267641), spatial transcriptomics were performed on 17 tissue samples from 4 patients, and bulk RNA-seq on multi-region tumour sectors from 91 patients. Analysis revealed extensive intra- and inter-tumour gene expression heterogeneity, identifying a specific subset of endothelial cells (ECs), INTS6+ ECs, enriched and spatially co-localized with tumour cells in primary tumours of recurrent cases. A significant ANGPTL4-SDC1 ligand-receptor interaction was found between INTS6+ ECs and tumour cells. Interestingly, INTS6+ ECs were enriched in histologically annotated microvascular invasion (MVI). These findings suggest novel therapeutic targets focusing on endothelial cell interactions within TME.
from sddb import Catalog
cohort = Catalog().collection("geo-gse281759")
cohort.members # the 17 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-gse281759")
coll.ordered_artifacts.to_dataframe() # the 17 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-gse281759 --dest data/ Licenses: 17 NCBI GEO policy
Cite this collection
doi.org/10.1016/j.jhepr.2026.101790 ↗@article{Seshachalam_2026,
title = {Multiomics and multi-region spatial transcriptome analysis reveal cellular networks and pathways associated with HCC recurrence},
volume = {8},
ISSN = {2589-5559},
url = {http://dx.doi.org/10.1016/j.jhepr.2026.101790},
DOI = {10.1016/j.jhepr.2026.101790},
number = {5},
journal = {JHEP Reports},
publisher = {Elsevier BV},
author = {Seshachalam, Veerabrahma P. and Sari, Ita N. and Toh, Kane and Majee, Prativa and Chong, Shay L. and Sekar, Karthik and Aiderus, Aziz and Idzham, Khaireen and Qi, Ong Y. and Chong, Li Y. and Caldez, Matias and Shanmugam, Raghuvaran and Ying, Dorcas H.H. and Lee, Esmond and Toh, Jiaying and Lele, Wu and Lee, Jia Y.J. and Zhong, Guorui and Chew, Sin C. and Chen, Gao B. and Wu, Lingyan and Chung, Alexander Y.F. and Cheow, Peng C. and Kam, Juinn H. and Kow, Alfred W.C. and Leow, Wei Q. and Jegannathan, Nagalakshmi and Chen, Kaina and Bunchaliew, Chairat and de Villa, Vanessa H. and Koh, Peng S. and Bonney, Glenn and Goh, Brian K.P. and Tam, Wai Leong and Loo, Lit-Hsin and Yeong, Joe and Tergaonkar, Vinay and Chow, Pierce K.H.},
year = {2026},
month = May,
pages = {101790}
}