GSE157020

TSG-6 supports fistulizing Crohn’s disease by a mechanoregulated activation of the epithelial-to-mesenchymal transition

Whole-study status Not suitable

Dataset does not meet the current suitability threshold.

Whole-study downloads — these do not apply your sample requirements.

Selected cohort requirements

Samples meeting selected requirements: 0 cases / 0 controls

View matching samples

30 case / 0 control samples elsewhere in the study have incomplete or conflicting evidence; they are not included above

Patient pairs verified in indexed sample metadata: 0

A case/control comparison meeting these requirements is not confirmed.

Counts describe samples, not independent patients. Pair verification uses explicit subject identifiers in indexed sample metadata. Zero verified pairs does not establish that the study is unpaired; reported matched-normal design alone is insufficient.

Summary

BACKGROUND AND AIMS: Perianal fistula represents one of the most important complications in Crohn’s Disease (CD). Epithelial-to-mesenchymal transition (EMT) has been demonstrated to play a major role in the pathogenesis, however the mechanisms driving EMT need to be clarified. Significant alterations in the tissue structural composition occur in the fistula, but how these changes promote EMT was not addressed. We aim to explore the relevance of TSG-6, a stabilizer of extracellular matrix, in the fistula pathogenesis. METHODS: Intestinal surgical specimens from perianal fistula tissue and surrounding region of fistulizing CD were analyzed histologically and by RNA sequencing (RNA-seq). Significantly modulated genes and TSG-6 expression were validated by RT-PCR, WB and immunofluorescence assays [N=20]. TSG-6 expression was reconstituted in Caco-2 cell line and primary perifistula-derived fibroblasts, and proliferative and migratory assays were performed. RESULTS: A marked different organization of extracellular matrix was found across fistula and perifistula regions with an increased expression of integrins, hyaluronan synthases, TSG-6 and MMPs in the fistula. TSG-6 overexpression in Caco-2 cells reduced proliferation, promoted the EMT transcription factor SNAIL, and, in co-stimulation with TGFβ1, migration. The acquisition of TSG-6 increased SNAI1 and hyaluronan synthases levels, and led to activated phenotype of perifistula-derived fibroblasts. Positive Pearson correlation was observed between TSG-6 expression and mechanosensitive proteins in fistula tissue. CONCLUSIONS: By mediating changes in the extracellular matrix organization, TSG-6 triggers the EMT transcription factor SNAIL through the activation of mechanosensitive proteins. These data point to TSG-6 as a new potential target for the treatment of perianal fistula.

Overall design

6x Healthy with fistule, 6x Healthy with perifistule, 9x Crohn's with fistule, 9x Crohn's with perifistule.

Source Evidence

4 sources
Source Contribution Status
GEO

Original dataset metadata, sample metadata, source links, and GEO data availability flags.

Sample records
30 GSM samples
Primary source
recount3

Planned trusted source for processed count availability.

No match found
Expression Atlas

Planned source for curated expression experiment links.

No match found
PubMed

Primary GEO citations and related PubMed articles that mention this dataset.

1 linked publication 1 DOI

Primary publication

  1. Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn's Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal Transition. Cellular and molecular gastroenterology and hepatology, 2023
Available

Metadata Quality Components

Analysis Readiness

Not ready
55% DE readiness

Contrast completeness

10/25 pts

Only one side of the contrast is present; downstream DE needs both groups.

Minimum group size

0/20 pts

Minimum group size cannot be evaluated until a complete contrast exists.

Processed data availability

20/20 pts

Processed data is marked available in the GEO index.

Sample decision clarity

15/15 pts

All samples are assigned to a case or control group.

Blocking warnings

0/10 pts

Critical warnings must be resolved before downstream analysis.

Metadata normalization

10/10 pts

Metadata quality is high enough to support downstream handoff.

Blockers

  • No complete case/control contrast is available.
  • Critical dataset warnings must be resolved.

Next Steps

  • Resolve critical warnings before downstream analysis.

Analysis Preparation Checklist

4/6 ready

Group labels reviewed

Blocked

No complete case/control grouping exists yet.

Review the sample grouping table and assign both case and control groups.

Minimum sample count met

Blocked

At least one group has fewer than 2 samples.

Choose a larger dataset or merge only scientifically valid groups.

Processed counts available

Ready

Processed data availability is marked true in the GEO index.

Verify that downloaded processed files contain usable count or expression identifiers.

Ambiguous samples handled

Ready

No review-needed or unassigned samples are present in the proposed grouping.

Review the grouping table for biologically meaningful differences that the automated checks may not detect.

Exclusion decisions recorded

Ready

No hard-excluded samples were detected by the current rules.

Record any manual exclusions in the downstream analysis notes.

Source traceability preserved

Ready

The dataset and sample accessions can be traced back to GEO.

Keep GEO accessions with exported metadata.

Bioinformatician Review

Bioinformatician review required

Ask a bioinformatician to review grouping, count availability, exclusions, and design before DE.

Analysis readiness has blockers that must be resolved before DE.

Analysis preparation checklist contains blocked items.

No complete case/control or treatment/control contrast is available.

At least one comparison group has fewer than two samples.

Critical dataset warnings are present.

Study design is model-system or unclear and should be reviewed before analysis.

Why This Is Ranked Here

Tumor vs normal
Not suitable Dataset does not meet the current suitability threshold.

Applied Review Decisions

No active review decisions affect this ranking.

Derived Classifications

  • Disease context Crohn's disease Disease context came from Normalization rules.
  • Likely case group Crohn's disease 30 samples
  • Likely control group No control group detected 0 samples

Intent Interpretation

  • Downgrade or exclusion reason Comparison: Unclear study design. Specimen: Biopsy. Comparison suitability: 0%. Derived from current-intent ranking reasons.

Ranking Facts

Supporting evidence

  • Prioritized assay: bulk RNA-seq is the active assay expectation.
  • Interpreted disease metadata: Crohn's disease.
  • Processed data is available for downstream review.
  • External evidence: PubMed links 1 publication; 1 DOI available: PMID 36521659.
  • Publication context: Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn's Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal Transition.. Cellular and molecular gastroenterology and hepatology, 2023. PMID 36521659. DOI 10.1016/j.jcmgh.2022.12.006.

Cautions

  • Comparison: Unclear study design. Specimen: Biopsy. Comparison suitability: 0%.
  • Downgraded for tissue search because study design or specimen source is unclear.
  • Unclear study design downgraded for patient tissue tumor-vs-normal search intent.
  • Missing or unclear metadata. Unclear study design downgraded for patient tissue tumor-vs-normal search intent.
  • Overall score capped because comparison suitability is weak for the selected search intent.
  • Missing or unclear metadata. Comparison - Unclear study design. Specimen - Biopsy. Comparison suitability: 0%.
  • Missing or unclear metadata. Downgraded for tissue search because study design or specimen source is unclear.
  • Comparison suitability score is below the Phase 1 recommended threshold.

Dataset Warnings

Normalized Fields

154 fields

Sample Group Preview

30 rows shown
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Study totals: Case 30 | Control 0 | Unassigned 0 | Excluded 0 | Ambiguous 0 30 rows shown
Group Role Accession Title Source / characteristics Reason
Crohn's disease Case GSM4750933 F2_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750934 F6_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750935 F8_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750936 F10_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750937 F14_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750938 F16_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750939 F20_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750940 F22_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750941 F26_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750942 PF2_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750943 PF6_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750944 PF7_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750945 PF8_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750946 PF10_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750947 PF16_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750948 PF20_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750949 PF22_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750950 PF26_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750951 F28_Non_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750952 F11_Non_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750953 F13_Non_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750954 F17_Non_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750955 F18_Non_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750956 F21_Non_CD.Fistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with fistule Case marker detected.
Crohn's disease Case GSM4750957 PF28_Non_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750958 PF11_Non_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750959 PF13_Non_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750960 PF17_Non_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750961 PF18_Non_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with perifistule Case marker detected.
Crohn's disease Case GSM4750962 PF21_Non_CD.Perifistule Ileum biopsy Tissue: Ileum biopsy; Diagnosis: Non-Crohn's disease with perifistule Case marker detected.

Use as Discovery Cohort

External Validation Finder

Carry Siftome's disease, organism, specimen, assay, data type, and accession into a validation project. Uncertain fields remain Unknown.