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PRAME-mediated retinoid resistance in keratinocyte carcinomas is overcome by EZH2 inhibition

GSE271108 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2025/03/17 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 36 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
Cutaneous squamous cell carcinomaThis series is part of our curated briefing on it.
Samples
36 samples: 12 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.
Paper
Targeting PRAME directly or via EZH2 inhibition overcomes retinoid resistance and represents a novel therapy for keratinocyte carcinomaMolecular oncology · 2025
Summary (written by the submitters)
Preferentially Expressed Antigen of Melanoma (PRAME) is a cancer-testis antigen that is expressed in subsets of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), collectively termed keratinocyte carcinomas (KC). PRAME functions as a transcriptional co-repressor of retinoid signaling by guiding enhancer of zeste homologue 2 (EZH2), a repressive histone methyltransferase, to retinoic acid response elements (RARE) found in gene promoters.
Read the full summary ↓
The functions and therapeutic relevance of PRAME expression in KC have not been investigated. In the present study, we evaluated the implications of PRAME expression upon KC development and response to retinoid-based therapeutics. High PRAME expression in tumors was negatively correlated with epidermal differentiation gene signatures. Similarly, PRAME overexpression (OE) downregulated epidermal differentiation gene signatures, and impaired epidermal differentiation. PRAME OE also attenuated retinoid-induced RARE activation, growth suppression and differentiation responses. Conversely, low-PRAME tumors and PRAME-depleted KC cells possessed enrichment of epidermal differentiation gene signatures. PRAME depletion also restored retinoid-induced RARE activation, suppression of KC growth, keratinization suppression in SCC cells and cell death signaling in BCC cells. Furthermore, EZH2 inhibitors potentiated the retinoid-induced RARE activation and suppress the growth of PRAME-expressing BCC and cSCC cells. We demonstrate that PRAME confers retinoid resistance in KC, and we contend that PRAME-mediated retinoid resistance in KC may be overcome by targeting EZH2.
Published in
Targeting PRAME directly or via EZH2 inhibition overcomes retinoid resistance and represents a novel therapy for keratinocyte carcinoma
Ramchatesingh B, Martinez Villarreal A, Lefrançois P et al. · Molecular oncology 2025 · PMID 40101298 · doi:10.1002/1878-0261.13820
This dataset
Open GSE271108 in finder → Find more human RNA-seq datasets → Cutaneous squamous cell carcinoma 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 GSE271108_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 PRJNA1129865 and SRA study SRP517020. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40101298) ↗
Study design
12 conditions, mostly in triplicate
KerCT_EV_DMSO_biol ×3 KerCT_EV_ATRA_biol ×3 KerCT_OE_DMSO_biol ×3 KerCT_OE_ATRA_biol ×3 CAL27_EV_DMSO_biol ×3 CAL27_EV_ATRA_biol ×3 CAL27_OE_DMSO_biol ×3 CAL27_OE_ATRA_biol ×3 +4 more

Supports a between-group comparison across 36 samples.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 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 Cutaneous squamous cell carcinoma datasets

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