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NOX4/NOX1 dual inhibition in cholangiocarcinoma as an effective approach to target TGF-beta protumorigenic actions in cancer associated fibroblasts

GSE274024 Homo sapiens (human) RNA-seq (gene expression) 45 samples Submitted 2025/07/21 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 45 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
CholangiocarcinomaThis series is part of our curated briefing on it.
Samples
45 samples: 15 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
NADPH oxidase 1/4 dual inhibition impairs transforming growth factor-beta protumorigenic effects in cholangiocarcinoma cancer-associated fibroblastsSignal transduction and targeted therapy · 2025
Summary (written by the submitters)
Transforming growth factor beta (TGF-β) signalling has become an attractive therapeutic target, due to its pro-tumorigenic actions on epithelial cells and its immunosuppressive effects in the tumour microenvironment. In intrahepatic cholangiocarcinoma (iCCA), a highly aggressive malignancy of the biliary tract with poor prognosis, the latest clinical trials using TGF-β inhibitors have failed indicating that the specific actions carried out by TGF-β in iCCA are yet not well delineated.
Read the full summary ↓
Here, we show that TGF-β signalling is highly active in iCCA and exerts a prominent suppressor effect on tumour cells, that relies on a functional canonical SMAD2/3/4 signalling. Thus, TGF-β inhibitors promote, instead of inhibit, tumour cell growth. NADPH oxidase 4 (NOX4), a downstream mediator of the TGF-β signalling pathway, is strictly expressed in cancer-associated fibroblasts (CAF) of iCCA and acts in concert with NOX1 to regulate CAF functions. Using a dual NOX4/NOX1 inhibitor impaired CAF actions and reduced tumour growth in vitro and in vivo. Collectively, our findings reveal an actionable way to specifically target TGF-β protumorigenic actions in CAF from iCCA without undesirable side effects on tumour cells.
Published in
NADPH oxidase 1/4 dual inhibition impairs transforming growth factor-beta protumorigenic effects in cholangiocarcinoma cancer-associated fibroblasts
Amengual J, Gonzalez-Sanchez E, Yáñez-Bartolome M et al. · Signal transduction and targeted therapy 2025 · PMID 40820091 · doi:10.1038/s41392-025-02347-z
This dataset
Open GSE274024 in finder → Find more human RNA-seq datasets → Cholangiocarcinoma landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE274024_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1144483 and SRA study SRP524380. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40820091) ↗
Study design
15 conditions, mostly in triplicate
HuCCT1-Vehicle-Sample ×3 HuCCT1-TGF-β1-Sample ×3 HuCCT1-Galunisertib-Sample ×3 RBE-Vehicle-Sample ×3 RBE-TGF-β1-Sample ×3 RBE-Galunisertib-Sample ×3 LX2-HSC-Vehicle-Sample ×3 LX2-HSC-Setanaxib-Sample ×3 +7 more

Supports a between-group comparison across 45 samples.

How we read this: 15 replicated groups read from 45 sample titles; they account for 45 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 5 more — browse all 45 samples with per-sample file links →

More Cholangiocarcinoma datasets

Search all human RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.