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An in vivo screening platform using PDX models reveals KEAP1, USP22 and other drivers of chemoresistance in small cell lung cancer

GSE255095 Homo sapiens (human) RNA-seq (gene expression) 67 samples Submitted 2025/03/11 Platform GPL16791Platform GPL30173
At a glance

RNA-seq (gene expression) · human · 67 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
Small cell lung cancerThis series is part of our curated briefing on it.
Samples
67 samples: 16 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
In vivo functional screens reveal KEAP1 loss as a driver of chemoresistance in small cell lung cancerScience advances · 2025
Summary (written by the submitters)
Small cell lung cancer (SCLC) is characterized by exquisite chemosensitivity followed by rapid emergence of chemoresistance. To identify genetic events that drive resistance to cisplatin-etoposide chemotherapy, we conducted cDNA overexpression and CRISPR knockout screens in an in vivo platform centered on chemosensitive patient derived xenograft (PDX) models of SCLC.
Read the full summary ↓
cDNA overexpression screens revealed MYC, MYCN and MYCL as drivers of tumor cell growth through chemotherapy. CRISPR knockout screens identified the KEAP1/NRF2 pathway and members of the SAGA (Spt-Ada-Gcn5 acetyltransferase) complex, including the deubiquitylase USP22. We demonstrated that knockout of either KEAP1 or USP22 switches chemosensitive PDX models to become chemoresistant, with our data supporting distinct molecular consequences of each, including suppression of DNA damage signaling upon USP22 deletion. Data from the IMpower133 clinical trial revealed that a substantial proportion of SCLC patients exhibit KEAP1/NFE2L2 genetic alterations, with activation of an NRF2 transcriptional signature associated with reduced SCLC patient survival with chemotherapy.
Published in
In vivo functional screens reveal KEAP1 loss as a driver of chemoresistance in small cell lung cancer
Brumage L, Best S, Hippe DS et al. · Science advances 2025 · PMID 40267200 · doi:10.1126/sciadv.adq7084
This dataset
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.

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 GSE255095_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1073511. Searching any of these in the dataset finder brings you back here.

Study design
16 conditions, mostly in triplicate
H14_Ctrlsg1_CE ×6 H14_Ctrlsg1_SAL ×6 H14_KEAP1g1_CE ×5 NCI109B_Ctrlsg1_SAL ×5 NCI109B_Ctrlsg1_CE ×5 NCI109B_USP22sg1_SAL ×5 NCI109B_USP22sg1_CE ×5 H14_KEAP1g1_SAL ×4 +10 more

Supports a between-group comparison across 65 samples.

How we read this: 16 replicated groups read from 67 sample titles; they account for 65 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

+ 27 more — browse all 67 samples with per-sample file links →

More Small cell lung cancer 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.