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NOTCH3 Blockade Inhibits Cancer Cell Plasticity through a NOTCH3/PD-L1 Oncogenic Axis in Triple Negative Breast Cancer

GSE236140 Homo sapiens (human) RNA-seq (gene expression) 27 samples Submitted 2024/06/28 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 27 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
Breast cancerThis series is part of our curated briefing on it.
Samples
27 samples: 27 × P25801Groups 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)
Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and mainly affects pre-menopausal and minority women. Therapeutic options are yet limited, in part because of acquisition of tumor cells with cancer stem cell (CSC) properties, leading to intrinsic resistance to chemotherapeutic agents and immune evasion capacity.
Read the full summary ↓
Dysregulated Notch signaling has been linked to breast cancer and in this study, we demonstrate the pivotal role of NOTCH3 in inducing the enrichment of chemoresistant ALDHhigh CSCs. Significantly, selective targeting of NOTCH3 with AV-353, a novel humanized monoclonal antibody, or by shRNA-mediated knockdown, impaired the enrichment of ALDHhigh CSCs with high self-renewal capacity, induced apoptosis and enhanced chemosensitivity. AV-353 treatment similarly reduced growth of xenografted tumors in vivo. Moreover, blocking NOTCH3 by AV-353 or shRNA reduced PD-L1 expression in TNBC cells, which was linked to the inhibition of tumor growth and enhancement of CD8+ T-cell infiltration. Taken together, these findings provide preclinical evidence for NOTCH3 as a novel therapeutic target in TNBC and reveal a novel NOTCH3/PD-L1 oncogenic axis as a platform for the betterment of TNBC therapy.
This dataset
Open GSE236140 in finder → Find more human RNA-seq datasets → Breast 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 GSE236140_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 PRJNA989131 and SRA study SRP446931. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
27 × P25801

Supports a between-group comparison across 27 samples.

How we read this: 1 replicated groups read from 27 sample titles; they account for 27 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 Breast cancer datasets

Search all human RNA-seq datasets in GEO →

Share this dataset

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.