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Metabolic Dependency on De Novo Pyrimidine Synthesis in Platinum Resistant Ovarian Cancer

GSE283381 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/10/10 Platform GPL18573
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: 3 × OVCAR5 cisplatin sensitive cells, control, vs 3 × OVCAR5 cisplatin sensitive cells, brequinar treatment, vs 3 × OVCAR5 cisplatin resistant cells, control, vs 3 × OVCAR5 cisplatin resistant cells, brequinar treatment,Groups 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
Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian CancerCancer research · 2026
Summary (written by the submitters)
Recurrent high grade serous ovarian cancer (OC) is mostly lethal due to development of resistance to platinum-based chemotherapy. We used cisplatin resistant (Cis-R) cells generated by repeat cisplatin treatment of sensitive (Cis-S) OC cell lines, and metabolomics to identify critical factors associated with platinum resistance. Pathway analysis of differentially abundant metabolites in Cis-R vs.
Read the full summary ↓
Cis-S OVCAR5 and COV362 cells identified enrichment of pyrimidine metabolism (FDR<0.05) produced by increased de novo pyrimidine synthesis which was subsequently confirmed by flux analysis. Inhibition of this pathway using the DHODH inhibitor brequinar (BRQ) decreased viability, and produced expression changes in genes of the mitochondrial electron transport in Cis-R compared with Cis-S cells. Oxygen consumption rate (OCR) measured with a Seahorse assay indicated lower (P<0.05) OCR (baseline, ATP-related, and maximal) and spare respiratory capacity (SRC) in Cis-R vs. Cis-S OVCAR5 cells. In addition, BRQ had dose-related inhibitory effects on OCR across assay conditions in both Cis-R and Cis-S cells, SRC however, was inhibited by BRQ only in Cis-R cells. In vivo, BRQ attenuated growth of intraperitoneal (ip) Cis-R tumor xenografts but did not alter Cis-S tumors. Similarly, tumor growth was inhibited (p<0.01) by BRQ in a Cis-R PDX model. BRQ plus carboplatin enhanced (p<0.05) the inhibitory effects of carboplatin alone on total tumor weight and numbers of Cis-R ip tumor xenografts. Results indicate that Cis-R cells develop mechanisms that enhance de novo pyrimidine synthesis and maintain relatively low levels of mitochondrial oxidation, however these changes make Cis-R cells vulnerable to inhibitors of these processes.
Published in
Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer
Cardenas H, Wang Y, Zhao G et al. · Cancer research 2026 · PMID 41091828 · doi:10.1158/0008-5472.CAN-25-0043
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 GSE283381_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 PRJNA1193543 and SRA study SRP549034. Searching any of these in the dataset finder brings you back here.

Study design
3 × OVCAR5 cisplatin sensitive cells, control, vs 3 × OVCAR5 cisplatin sensitive cells, brequinar treatment, vs 3 × OVCAR5 cisplatin resistant cells, control, vs 3 × OVCAR5 cisplatin resistant cells, brequinar treatment,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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 Ovarian cancer datasets

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