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Genetic Alterations in KEAP1-NRF2 system Induced by Anti-Cancer Treatments Contribute to Cisplatin Resistance in Head and Neck Squamous Cell Carcinoma

GSE293361 Homo sapiens (human) RNA-seq (gene expression) 42 samples Submitted 2025/12/02 Platform GPL28038
At a glance

RNA-seq (gene expression) · human · 42 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
Head and neck cancerThis series is part of our curated briefing on it.
Samples
42 samples
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
Cisplatin-induced genetic alterations in KEAP1 promote therapeutic resistance in head and neck squamous cell carcinomaRedox biology · 2025
Summary (written by the submitters)
Cisplatin (CDDP) is widely used in the chemotherapy of head-and-neck squamous cell carcinoma (HNSCC), but its efficacy is limited in recurrent cases. This highlights the need for a deeper understanding of the mechanisms underlying the CDDP resistance. We hypothesized that chemoradiotherapy with CDDP may induce hyperactivation of NRF2, contributing to CDDP resistance.
Read the full summary ↓
To investigate this, we first examined NRF2 expression in clinical HNSCC samples by immunohistochemistry and assessed the occurrence of somatic mutations in KEAP1 and NRF2 genes using public databases. We found that high NRF2 expression was associated with poorer prognosis compared to low expression. Furthermore, recurrent HNSCC cases following post-operative chemoradiotherapy exhibited higher NRF2 accumulation than their corresponding primary tumors. Database analysis also revealed occurrence of frequent mutations in KEAP1 associated with CDDP treatment. We then assessed the role of NRF2 in HNSCC malignancy utilizing seven parent (P) HNSCC cell lines and their CDDP-resistant (CR) derivatives. Of these P-CR pairs, three CR cell lines exhibited NRF2 upregulation. Two of them carried KEAP1 mutations and one carried an NRF2 mutation, both present in P and CR lines. These NRF2-high CR lines showed elevated expression of NRF2 target gene and activation of xenobiotic metabolism and reactive oxygen species pathways. Treatment with mitomycin C (MMC), known for its synthetic lethal activity against NRF2-activated cancer cells, showed strong cytotoxicity in NRF2-high CR lines. These findings indicate that the KEAP1-NRF2 system plays a critical role in the development of CDDP resistance and that MMC represents a promising therapeutic option for NRF2-high/CDDP-resistant HNSCC.
Published in
Cisplatin-induced genetic alterations in KEAP1 promote therapeutic resistance in head and neck squamous cell carcinoma
Nakayama Y, Taguchi K, Wakamori S et al. · Redox biology 2025 · PMID 40834643 · doi:10.1016/j.redox.2025.103819
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 GSE293361_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 PRJNA1244264 and SRA study SRP575333. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 42 more — browse all 42 samples with per-sample file links →

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