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The melanocytic transcriptomic state is independently associated with poor overall survival in long term follow up of patients with metastatic melanoma

GSE325123 Homo sapiens (human) RNA-seq (gene expression) 272 samples Submitted 2026/03/24 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 272 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
MelanomaThis series is part of our curated briefing on it.
Samples
272 samples: 23 conditions, mostly with about 12 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)
Introduction: Advanced cutaneous melanoma shows substantial heterogeneity in clinical outcomes, even among patients classified within the same clinical stage. Understanding the molecular drivers underlying this heterogeneity is critical for advancing treatment strategies. Previous studies have identified distinct melanoma transcriptomic states - Tirosh et al.
Read the full summary ↓
and Balderson et al. have agreed on a four-subtype model defining “Undifferentiated/AP1”, “Neural Crest/AP2”, “Transitory”, and “Melanocytic” states. However, their biological and clinical relevance remains unclear. Here we profiled in-transit melanoma (ITM) using digital spatial RNA profiling to associate melanoma transcriptomic states with overall survival (OS) and acral melanoma (AM) status. Methods: Digital spatial profiling (Nanostring GeoMx Whole Transcriptome Atlas) was performed across a tissue microarray constructed from patients with ITM diagnosed from 1990-2020. After filtering poor quality areas of interest (AOIs), we processed the data using noise correction and quantile normalization. We applied Principal Component Analysis (PCA) to define melanoma subtype signatures by ranking genes contributing to each of the first four PCs. We performed gene set enrichment analysis using GSEA with significance defined as an adjusted p-value < 0.05. Association between gene or gene-set expression and overall survival was evaluated using optimal expression cutoffs to define high and low groups, with a minimum group size of 20% to avoid overfitting. Cox proportional hazards models were then used to assess survival differences between groups. Results: We analyzed a cohort of 84 patients (116 AOIs) with ITM passing spatial transcriptomic QC. PCA of transcriptional profiles revealed distinct transcriptional states. The PC1 axis differentiated Transitory from Undifferentiated melanoma, PC2 reflected immune cell infiltration, PC3 corresponded to stromal cells and Neural crest-like melanoma, and PC4 associated with Melanocytic melanoma. We derived gene sets from the PCA results and associated the expression of each gene set with OS. Across a cohort of treatment-naïve ITM, high expression of the melanocytic state conferred a median overall survival difference of 7.59 years and independently associated with poor survival in multivariate analysis. AMs showed higher melanocytic state gene expression compared to non-acral cases. These findings were validated in external datasets, supporting that the melanocytic state predicts poor prognosis. Conclusion: The melanocytic transcriptional state was independently associated with worse overall survival in patients with metastatic melanoma and was enriched in acral melanoma, suggesting that assessment of the melanocytic state may have value for clinical risk stratification.
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 GSE325123_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 PRJNA1438670 and SRA study SRP684506. Searching any of these in the dataset finder brings you back here.

Study design
23 conditions, mostly with about 12 replicates each
Melanoma, A-A ×12 Melanoma, A-B ×12 Melanoma, A-C ×12 Melanoma, A-D ×12 Melanoma, A-E ×12 Melanoma, A-F ×12 Melanoma, A-G ×12 Melanoma, A-H ×12 +15 more

Supports a between-group comparison across 272 samples.

How we read this: 23 replicated groups read from 272 sample titles; they account for 272 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

+ 232 more — browse all 272 samples with per-sample file links →

More Melanoma datasets

Search all human RNA-seq datasets in GEO →

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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.