GEO series

FLASH proton radiotherapy mitigates inflammatory and fibrotic pathways and preserves cardiac function in a preclinical mouse model of radiation-induced heart disease

GSE261367 Mus musculus (mouse) RNA-seq (gene expression) 11 samples Submitted 2024/07/11 Platform GPL15103

At a glance

RNA-seq (gene expression) · mouse · 11 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: Mus musculus (mouse)
Samples: 11 samples: 4 × N vs 4 × S-PRT vs 3 × F-PRTGroups 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: FLASH Proton Radiation Therapy Mitigates Inflammatory and Fibrotic Pathways and Preserves Cardiac Function in a Preclinical Mouse Model of Radiation-Induced Heart DiseaseInternational journal of radiation oncology, biology, physics · 2024

Summary (written by the submitters)

Purpose: Studies during the past 9 years suggest that delivering radiation at dose rates exceeding 40 Gy/s, known as “FLASH” radiotherapy, enhances the therapeutic index of radiation therapy (RT) by decreasing normal tissue damage while maintaining tumor response compared to conventional (or standard) RT. This study demonstrates the cardioprotective benefits of FLASH proton RT (F-PRT) compared to standard (conventional) proton RT (S-PRT), as evidenced by reduced acute and chronic cardiac toxicities.

Read the full summary ↓

Methods and Materials: Mice were imaged using cone beam computed tomography to precisely determine the heart’s apex as the beam isocenter. Irradiation was conducted utilizing a shoot-through technique with a 5mm collimator. Bulk RNA-sequencing was performed on non-irradiated (NR) samples, as well as apexes treated with F-PRT or S-PRT, at 2 weeks following a single 40 Gy dose. Inflammatory responses were assessed through multiplex cytokine/chemokine microbead assay and immunofluorescence analyses. Levels of perivascular fibrosis were quantified using Masson’s Trichrome and Picrosirius red staining. Additionally, cardiac tissue functionality was evaluated by 2D echocardiograms at 8 and 30 weeks post-PRT. Results: Radiation damage was specifically localized in the heart’s apex. RNA profiling of cardiac tissues treated with PRT revealed that S-PRT induced unique pathways associated with DNA damage response, induction of tumor necrosis factor superfamily and inflammatory response, while F-PRT primarily affected cytoplasmic translation, mitochondrion organization and ATP synthesis. Notably, F-PRT led to a milder inflammatory response, accompanied by significantly attenuated changes in TGF-1 and SMA levels. Critically, F-PRT decreased collagen deposition, and better preserved cardiac functionality compared to S-PRT. Conclusions: This study demonstrated that F-PRT reduces the induction of an inflammatory environment with lower expression of inflammatory cytokines and profibrotic factors. Importantly, the results indicate that F-PRT better preserves cardiac functionality, as confirmed by echocardiography analysis, while also mitigating the development of long-term fibrosis.

Published in

FLASH Proton Radiation Therapy Mitigates Inflammatory and Fibrotic Pathways and Preserves Cardiac Function in a Preclinical Mouse Model of Radiation-Induced Heart Disease

Kim K, Kim MM, Skoufos G et al. · International journal of radiation oncology, biology, physics 2024 · PMID 38364948 · doi:10.1016/j.ijrobp.2024.01.224

This dataset

Open GSE261367 in finder → Find more mouse RNA-seq datasets →

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 GSE261367_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 PRJNA1086574 and SRA study SRP494633. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38364948) ↗

Study design

4 × N vs 4 × S-PRT vs 3 × F-PRT

Supports a between-group comparison across 11 samples.

How we read this: 3 replicated groups read from 11 sample titles; they account for 11 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

GSM8141479 NR1 N
GSM8141480 NR2 N
GSM8141481 NR3 N
GSM8141482 NR4 N
GSM8141483 S-PRT1 S-PRT
GSM8141484 S-PRT2 S-PRT
GSM8141485 S-PRT3 S-PRT
GSM8141486 S-PRT4 S-PRT
GSM8141487 F-PRT2 F-PRT
GSM8141488 F-PRT3 F-PRT
GSM8141489 F-PRT4 F-PRT

Datasets on a similar topic

GSE307570 Localized FLASH Radiotherapy Reduces Long-Term Skin and Muscle Damage While Preserving Systemic Homeostasis 20 samples shares flash, radiotherapy
GSE326864 Differential impact of FLASH and conventional radiotherapy on a pivotal metabolic organ: White Adipose Tissue 10 samples shares flash, radiotherapy
GSE283273 Urolithin A Provides Cardioprotection and Mitochondrial Quality Enhancement Preclinically and Improves Cardiovascular Health Biomarkers in Humans [mouse_cardiac_aging] 18 samples shares preclinical, cardiac
GSE205025 The lower the better? Impact of radiation dose reduction on radiation-induced lung fibrosis molecular signature: approach towards preclinical model perfection 17 samples shares radiation-induced, preclinical
GSE277443 EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress [ER-stress RNA-seq] 10 samples shares radiation-induced, preserves
GSE246261 Asparagine endopeptidase deficiency mitigates radiation-induced brain injury by suppressing microglia-mediated neuronal senescence 6 samples shares radiation-induced, mitigates
GSE277445 EMP1 preserves hematopoietic stem cell potential under homeostasis and radiation-induced injury by alleviating ER stress 22 samples shares radiation-induced, preserves
GSE338640 Vascular function underlies enhanced intestinal regeneration after FLASH radiation 26 samples shares flash

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.