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Tumor-derived Apolipoprotein E induces Tip endothelial cell to remodel tumor stroma ratio and promote pancreatic neuroendocrine tumor progression

GSE296486 Homo sapiens (human) Single-cell RNA-seq 34 samples Submitted 2025/05/13 Platform GPL34284
At a glance

Single-cell RNA-seq · human · 34 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
34 samples: 9 conditions, mostly with about 4 replicates eachGroups 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)
A low tumor stroma ratio (TSR) in patients with pancreatic neuroendocrine tumors (pNETs) is associated with a significantly poorer tumor prognosis. However, current clinical trials have shown that administration of a single drug targeting a matrix component does not improve tumor prognosis. The investigation of treatments targeting matrix components in combination with other therapies is crucial for effectively managing the TSR in pNETs.
Read the full summary ↓
LCM analysis revealed that stroma-rich tumors excessively secrete APOE relative to stroma-poor tumors, with the specific receptor SCARB1 predominantly located on ECs. Single-cell analysis revealed a greater proportion of endothelial tip cells (TipECs) in stroma-rich tumors, because tumor-derived APOE could induce the transformation of other types of ECs into TipECs. These TipECs played crucial roles in driving pNETs progression by facilitating cancer-associated fibroblasts (CAFs) recruitment and remodeling the TSR. Mechanistically, APOE promoted the uptake of palmitic acid by ECs, and subsequently activated the transcription factor ATF6 to promote the PDGF pathway in vitro. Clinically, screening of 6 commonly used drugs for pNETs in vivo revealed that treatment with mTOR inhibitors suppressed the secretion of APOE by tumor cells and the subsequent effects of APOE on the stromal microenvironment, including the proportions of TipECs and CAFs. Importantly, mTOR inhibitors synergistically enhanced the effects of stroma-targeting PEGPH20 in vivo in pNETs. Overall, our study revealed that tumor-derived APOE could induce TipECs to remodel the TSR, and that mTOR inhibitors could increase the efficacy of the stroma-targeting drug PEGPH20.
This dataset
Open GSE296486 in finder → Find more human 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 GSE296486_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1256750 and SRA study SRP583009. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
9 conditions, mostly with about 4 replicates each
Effect of PBS treatment on subcutaneous tumor… ×4 Effect of rapamycin treatment on subcutaneous… ×4 Effect of octreotide treatment on subcutaneou… ×4 Effect of surufatinib treatment on subcutaneo… ×4 Effect of sunitinib treatment on subcutaneous… ×4 Effect of temozolomide treatment on subcutane… ×4 Effect of everolimus treatment on subcutaneou… ×4 48-hour treatment of HUVECs with DMSO ×3 +1 more

Supports a case/control comparison: 28 samples read as cases, 3 as controls.

How we read this: 9 replicated groups read from 34 sample titles; they account for 34 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
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