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PAD2-Mediated Histone Citrullination Drives Tumor Progression by Enhancing Cell Proliferation and Modifying the Microenvironment in Pancreatic Cancer

GSE281497 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/06/30 Platform GPL24676
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
Pancreatic cancerThis series is part of our curated briefing on it.
Samples
12 samples: 6 conditions, mostly in duplicateGroups 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)
Histone citrullination is catalyzed by peptidyl arginine deiminases (PAD) that play a role in gene regulation. However, the clinical significance and molecular mechanisms of histone citrullination and PADs in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aimed to investigate the role and potential molecular mechanisms of PADs in PDAC.
Read the full summary ↓
Histone citrullination was upregulated and strongly associated with PAD2 nuclear expression in human PDAC samples. PAD2 nuclear expression correlated with aggressive tumor characteristics and poor prognosis. PAD2 overexpression increased PDAC cell proliferation, whereas its knockdown had the opposite effect in vitro. PAD2 bound to the promoter regions of PRUNE1 and E2F1, resulting in the activation of their mRNA expression via upregulation of histone citrullination and chromatin accessibility at their promoter regions. PAD2 overexpression enhanced tumorigenicity, and increased PRUNE1 expression and M2 tumor-associated macrophage (M2 TAM) infiltration in subcutaneous and orthotopic PDAC models. In vitro assay showed that macrophages cultured in a conditioned medium from PAD2-expressing PDAC cells exhibited an increase of M2 TAM-related markers in a PRUNE1-dependent manner. Treatment with the PAD2 inhibitors Cl-amidine and AFM-30a selectively impaired the growth and tumorigenicity of PAD2-expressing PDAC cells in vitro and in vivo. Furthermore, the triple-high expression of nuclear PAD2, PRUNE1, and the M2 TAM marker CD206 may serve as independent adverse prognostic factors for human PDAC. Conclusively, PAD2-mediated histone citrullination drives PDAC progression by epigenetically regulating downstream target genes and influencing the tumor microenvironment. The PAD2-PRUNE1-M2 TAM axis may be a promising therapeutic target and prognostic indicator for PDAC.
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 GSE281497_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 PRJNA1184148 and SRA study SRP544223. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in duplicate
AsPC1_GFP ×2 AsPC1_PADI2 ×2 KLM1_NC ×2 KLM1_siPADI2 ×2 PANC1_NC ×2 PANC1_siPADI2 ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 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 Pancreatic cancer datasets

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