GEO series

Targeting USP8 Causes Synthetic Lethality through Degradation of FGFR2 in ARID1A-Deficient Ovarian Clear Cell Carcinoma

GSE273150 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/03/12 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 12 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: Ovarian cancerThis series is part of our curated briefing on it.
Samples: 12 samples
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: Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinomaNPJ precision oncology · 2025

Summary (written by the submitters)

Over half of ovarian clear cell carcinoma (OCCC) cases exhibit deficiencies in the ARID1A gene, a chromatin remodeling complex component. OCCC is resistant to chemotherapy and challenging to treat, necessitating new drug treatment strategies. This study used a publicly available dependency factor database to identify synthetic lethal targets for ARID1A-deficient cancer.

Read the full summary ↓

The DepMap portal was used to identify genes on which ARID1A-deficient cancer cell lines are highly dependent. Our analysis limited to ovarian cancer cell lines only identified the deubiquitinating enzyme USP8 as a synthetic lethal target in ARID1A-deficient OCCC cancer cell lines and mouse xenograft models. In addition, USP8 inhibitors were more selective for ARID1A-deficient cells than existing candidate drugs used in promising clinical trials for ARID1A-deficient cancers. Suppression of USP8 in ARID1A-deficient cells led to degradation of FGFR2 via the proteasome. Deficiency of ARID1A causes abnormalities in the STAT3 pathway, which is one of the downstream pathways of FGFR2, but suppression of USP8 attenuates phosphorylation of STAT3 pT705 and induces apoptosis. Taken together, the data suggest that USP8 is a novel therapeutic target for ARID1A-deficient OCCC and that it suppresses FGFR2-STAT3 signaling.

Published in

Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinoma

Saito R, Fukushima M, Sasaki M et al. · NPJ precision oncology 2025 · PMID 40074856 · doi:10.1038/s41698-025-00850-8

This dataset

Open GSE273150 in finder → Find more human RNA-seq datasets → Ovarian cancer 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 GSE273150_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 PRJNA1140249 and SRA study SRP522286. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40074856) ↗

Samples in this study

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+ 12 more — browse all 12 samples with per-sample file links →

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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.