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CRISPR Screens Identify the ATPase VCP as a Druggable Therapeutic Vulnerability in Cholangiocarcinoma

GSE305958 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2025/08/27 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 14 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
14 samples: 4 × HuCCT1_Veh vs 4 × RBE_Veh vs 3 × HuCCT1_CB5339 vs 3 × RBE_CB5339Groups 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
CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinomaProceedings of the National Academy of Sciences of the United States of America · 2025
Summary (written by the submitters)
Cholangiocarcinoma (CCA) remains a lethal malignancy with limited therapeutic options. Through genome-wide CRISPR-Cas9 screening, we identified the ATPase valosin-containing protein (VCP) as a critical dependency in CCA. Compound screens revealed that the VCP inhibitor CB-5339 potently suppresses CCA proliferation in a panel of patient derived organoids by inducing cellular senescence.
Read the full summary ↓
It is known that senescent cells persist and this can contribute to therapy resistance. To address this, we combined CB-5339 with senolytic agents (ABT-263 and conatumumab), which selectively eliminate senescent CCA cells, achieving enhanced tumor suppression in vitro and in vivo. Clinical analysis showed that VCP overexpression in CCA patients correlates with poor prognosis. Our study unveils a “one-two punch” strategy, targeting VCP-mediated senescence followed by senolytic clearance, offering a promising therapeutic approach for CCA.
Published in
CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma
Yang W, Wang S, Ji S et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 40991439 · doi:10.1073/pnas.2519568122
This dataset
Open GSE305958 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 GSE305958_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 PRJNA1308526 and SRA study SRP610371. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40991439) ↗
Study design
4 × HuCCT1_Veh vs 4 × RBE_Veh vs 3 × HuCCT1_CB5339 vs 3 × RBE_CB5339

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 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
More Cholangiocarcinoma datasets

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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.