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Genomic and Transcriptomic Analyses of Chemical Hepatocarcinogenesis Aggravated by Loss of Oncoproteins in Hepatocytes [RNA-Seq]

GSE246914 Mus musculus (mouse) RNA-seq (gene expression) 105 samples Submitted 2024/08/13 Platform GPL13112
At a glance

RNA-seq (gene expression) · mouse · 105 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
105 samples: 30 conditions, mostly with about 4 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)
Background and Aims: The chemical carcinogen diethylnitrosamine (DEN) is often used to induce HCC in mice. Curiously, several labs have reported that the removal of oncoproteins from hepatocytes exacerbated DEN induced HCC, with mechanisms unknown. This study aimed at deciphering molecular mechanisms underlying the tumor suppressive effect of oncoproteins.
Read the full summary ↓
Approach and Results: We generated mutant mouse lines with hepatocyte-specific deletions of Met, Ptpn11/Shp2, Ikkβ, or ctnnb1/β-catenin and assessed DEN-induced tumorigenesis in the wild-type and mutant mice. To systematically examine genetic and molecular signaling alternations, we performed whole exome and RNA-sequencing on liver samples collected at the pre-cancer and established cancer stages. Although the mutational profiles of DEN-induced tumors were barely different in wild-type and mutant mice, oncoprotein ablation increased DEN-induced mutational burdens, especially in Shp2-deficient tumors. RNA-sequencing revealed multiple changes in signaling pathways, in particular, upregulated epithelial-mesenchymal transition, cell migration, and tumor metastasis, as well as downregulated small molecule metabolism that was affected by oncoprotein ablation. We identified key molecules and pathways that are associated with hepatic innate immunity and implicated in liver tumorigenesis. In addition, we unveiled markedly changed expression of a few miRNAs in the human HCC database. Conclusions: The aggravation of DEN-induced HCC progression seen on oncoprotein ablation could be caused by common and distinct genomic and signaling alterations. This study reveals a new level of complexity in hepatocarcinogenesis and elucidates molecular mechanisms underlying tumor evolution and recurrence.
This dataset
Open GSE246914 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 GSE246914_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 PRJNA1035097 and SRA study SRP469958. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
30 conditions, mostly with about 4 replicates each
grp1_DEN_IKO_1m ×4 grp1_DEN_IKO_3m ×4 grp1_DEN_IKO_5m ×4 grp1_DEN_IKO_8m_NT ×4 grp1_DEN_IKO_8m_T ×4 grp1_DEN_SKO_1m ×4 grp1_DEN_SKO_3m ×4 grp1_DEN_SKO_5m ×4 +22 more

Supports a between-group comparison across 105 samples.

How we read this: 30 replicated groups read from 105 sample titles; they account for 105 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

+ 65 more — browse all 105 samples with per-sample file links →

Datasets on a similar topic

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