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Noncanonical role of NCOR1 as a facilitator of DNA mismatch repair and its deficiency sensitizes cancers to immune checkpoint blockade therapy

GSE290464 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2025/03/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 18 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
Mus musculus (mouse)
Samples
18 samples: 6 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.
Summary (written by the submitters)
Tumor genomic heterogeneity significantly influences the efficacy of immune checkpoint blockade (ICB) therapy. To elucidate the underlying mechanisms, we pioneered the development of an ICB response score (IRS) based on machine learning analysis of microenvironmental features. Through a pan-cancer genomic screening, we identified the nuclear receptor corepressor NCOR1 as a key regulator, the tumors with genomic deficiency of which display a tumor infiltrating lymphocyte (TIL)-inflamed microenvironment.
Read the full summary ↓
Genetic ablation of Ncor1 delays the tumorigenesis and metastasis in syngeneic and spontaneous tumor models in immunocompetent mice. Mechanistically, NCOR1 guards DNA mismatch repair by directly interacting with MSH2 and recruiting MutSa to chromatin for mismatch recognition, independent of its transcriptional regulatory activity coupling with histone deacetylase. Ncor1 depletion in hepatocellular carcinoma and melanoma cells promotes tumor immunogenicity by increasing tumor mutation burden (TMB), neoantigen load, and TIL infiltration and activation, thereby enhancing anti-PD-1 therapy efficacy. Our findings reveal that NCOR1 loss represents a novel mechanism underlying TMB-high tumors with intact MMR components, broadening the application of ICB.
This dataset
Open GSE290464 in finder → Find more mouse RNA-seq datasets →
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 GSE290464_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 PRJNA1228118 and SRA study SRP566250. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
6 conditions, mostly in triplicate
Hepa1-6, sgCtrl ×3 Hepa1-6, sgNcor1-1 ×3 Hepa1-6, sgNcor1-2 ×3 B16, sgCtrl ×3 B16, sgNcor1-1 ×3 B16, sgNcor1-2 ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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
Datasets on a similar topic

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