GSE25220

Transcription levels in human colon biopsies in IBS and IBD patients before and after participating in a high red-meat dietary intervention

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

25 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.

Source
GEO
Assay
microarray
Organism
Homo sapiens
Whole-study samples
44 samples
Specimen
Tissue
Reported/interpreted study design
Unclear study design Design classification does not establish patient pairs.
Comparison type
Tumor vs normal
Contributors
Hebels DG, Sveje KM, de Kok MC, van Herwijnen MH, Kuhnle GG, Engels LG, Vleugels-Simon CB, Mares WG, Pierik M, Masclee AA, Kleinjans JC, de Kok TM, Hebels D
Contact name
Dennie Hebels
Submission date
2010-11-09
Last update
2019-01-23
Organization
Maastricht University
Department
Health Risk Analysis and Toxicology
Public date
2011-02-01
Experiment types
Expression profiling by array
Platforms
GPL6480 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)
Series type
Series
SubSeries
Not available
BioProject
PRJNA134457

Summary

Study 1: Transcriptomic profiles in colon tissue from inflammatory bowel diseases patients in relation to N-nitroso compound exposure and colorectal cancer risk Study 1: N-nitroso compounds (NOC) have been suggested to play a role in human cancer development but definitive evidence is still lacking. In this study we investigated gene expression modifications induced in human colon tissue in relation to NOC exposure to gain insight in the relevance of these compounds in human colorectal cancer (CRC) development. Since there are indications that inflammation stimulates endogenous NOC formation, the study population consisted of patients with inflammatory bowel disease (IBD) and irritable bowel syndrome patients as controls without inflammation. Strong transcriptomic differences were identified in colonic biopsies from IBD patients and compared to controls that enhance the understanding of IBD pathophysiology. However, fecal NOC levels were not increased in IBD patients, suggesting that inflammation did not stimulate NOC formation. By relating gene expression changes of all subjects to fecal NOC levels, we did, however, identify a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending the molecular basis of NOC-induced carcinogenesis. We conclude that NOC exposure is associated with gene expression modifications in the colon that may increase CRC risk in humans. Study 2: Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon Study 2: Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat intake on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to transcriptomic changes induced in colonic tissue. In order to evaluate the potential effect of an inflamed colon on endogenous nitrosation, the study population consisted of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) control subjects without inflammation. The intervention had no effect on fecal NOC formation but fecal water genotoxicity significantly increased in response to red meat intake. Since IBD patients showed no difference in fecal NOC formation or fecal water genotoxicity levels as compared to IBS controls, for transcriptomic analyses, all subjects were grouped together. Genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated that are known to play a part in the carcinogenic process in the human colon. These results are in line with a possible oxidative effect of dietary heme. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a possible risk of CRC development in humans.

Overall design

The study investigated transcription levels in human colon biopsies obtained during a colonoscopic exam in 32 subjects suffering from either inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS). IBS patients served as control patients for comparison with IBD patients (see Study 1). 12 of these patients (6 IBD and 6 IBS) also followed a 7-day diet high in red meat (300 grams/day) after which a second colonscopic exam was performed to obtain colon biopsies to investigate the effect of the red meat intervention (Study 2). For each subject, cRNA copies of mRNA isolated from the colon biopsies were labeled with one dye (Cy3) and each sample was hybridized on a separate array. One replicate per subject or before/after red meat intervention (so 44 arrays in total, i.e. 20 before patients and 12 before and after patients).

Source Evidence

4 sources
Source Contribution Status
GEO

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

Sample records
44 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. N-nitroso compound exposure-associated transcriptomic profiles are indicative of an increased risk for colorectal cancer. Cancer letters, 2011
Available

Metadata Quality Components

Persisted metadata quality

93 pts
Clarity
93%
Weight
100 pts

Sample source clarity: All samples have source metadata and clear GSE/GSM accessions. Group clarity: Only one side of the comparison is clearly grouped. Disease clarity: Disease or condition metadata normalized. Tissue clarity: Anatomical source metadata normalized. Treatment clarity: No unclear treatment split detected in the sample metadata. Replicate clarity: No pooled sample or technical replicate flags detected. Data availability clarity: Dataset-level processed or raw data availability is explicit.

Analysis Readiness

Not ready
43% 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

3/15 pts

Unassigned or review-needed samples remain before analysis.

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.
  • 19 samples are still unassigned.
  • Critical dataset warnings must be resolved.

Next Steps

  • Resolve unassigned or review-needed samples in the grouping table.
  • Resolve critical warnings before downstream analysis.

Analysis Preparation Checklist

3/6 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

Needs review

0 review-needed samples and 19 unassigned samples remain.

Resolve ambiguous and unassigned samples before finalizing the contrast.

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.

One or more samples are unassigned and need manual grouping decisions.

Critical dataset warnings are present.

Assay context may require expert handling before DESeq2-style analysis.

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

  • Assay differs from search intent Microarray Search intent expects bulk RNA-seq. Assay came from Normalization rules.
  • Disease context Colorectal cancer, inflammatory bowel disease Disease context came from Normalization rules.
  • Likely case group Inflammatory bowel disease 25 samples
  • Likely control group No control group detected 0 samples

Intent Interpretation

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

Ranking Facts

Supporting evidence

  • Interpreted disease metadata: Colorectal cancer, Inflammatory bowel disease.
  • Processed data is available for downstream review.
  • External evidence: PubMed links 1 publication; 1 DOI available: PMID 21669488.
  • Publication context: N-nitroso compound exposure-associated transcriptomic profiles are indicative of an increased risk for colorectal cancer.. Cancer letters, 2011. PMID 21669488. DOI 10.1016/j.canlet.2011.05.007.

Cautions

  • Comparison: Unclear study design. Specimen: Tissue. Comparison suitability: 0%.
  • Downgraded for tissue search because study design or specimen source is unclear.
  • Downgraded assay: microarray cohorts are separated from the RNA-seq intent.
  • 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 - Tissue. 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

118 fields

Sample Group Preview

44 rows shown Show Hide
Study totals: Case 25 | Control 0 | Unassigned 19 | Excluded 0 | Ambiguous 0 44 rows shown
Group Role Accession Title Source / characteristics Reason
Inflammatory bowel disease Case GSM620750 Subject2_before Human colon biopsies before intervention Subject number: Subject2; Disease status: IBD; Gender: Male; Age: 57; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620751 Subject2_after Human colon biopsies after intervention Subject number: Subject2; Disease status: IBD; Gender: Male; Age: 57; Intervention status: After Case marker detected.
Inflammatory bowel disease Case GSM620755 Subject5_before Human colon biopsies before intervention Subject number: Subject5; Disease status: IBD; Gender: Male; Age: 72; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620756 Subject6_before Human colon biopsies before intervention Subject number: Subject6; Disease status: IBD; Gender: Male; Age: 60; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620757 Subject6_after Human colon biopsies after intervention Subject number: Subject6; Disease status: IBD; Gender: Male; Age: 60; Intervention status: After Case marker detected.
Inflammatory bowel disease Case GSM620762 Subject9_before Human colon biopsies before intervention Subject number: Subject9; Disease status: IBD; Gender: Male; Age: 31; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620763 Subject9_after Human colon biopsies after intervention Subject number: Subject9; Disease status: IBD; Gender: Male; Age: 31; Intervention status: After Case marker detected.
Inflammatory bowel disease Case GSM620764 Subject10_before Human colon biopsies before intervention Subject number: Subject10; Disease status: IBD; Gender: Female; Age: 48; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620765 Subject10_after Human colon biopsies after intervention Subject number: Subject10; Disease status: IBD; Gender: Female; Age: 48; Intervention status: After Case marker detected.
Inflammatory bowel disease Case GSM620766 Subject11_before Human colon biopsies before intervention Subject number: Subject11; Disease status: IBD; Gender: Male; Age: 54; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620767 Subject12_before Human colon biopsies before intervention Subject number: Subject12; Disease status: IBD; Gender: Male; Age: 71; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620768 Subject12_after Human colon biopsies after intervention Subject number: Subject12; Disease status: IBD; Gender: Male; Age: 71; Intervention status: After Case marker detected.
Inflammatory bowel disease Case GSM620770 Subject15_before Human colon biopsies before intervention Subject number: Subject15; Disease status: IBD; Gender: Male; Age: 29; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620771 Subject16_before Human colon biopsies before intervention Subject number: Subject16; Disease status: IBD; Gender: Male; Age: 29; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620776 Subject20_before Human colon biopsies before intervention Subject number: Subject20; Disease status: IBD; Gender: Female; Age: 55; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620779 Subject23_before Human colon biopsies before intervention Subject number: Subject23; Disease status: IBD; Gender: Male; Age: 53; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620780 Subject24_before Human colon biopsies before intervention Subject number: Subject24; Disease status: IBD; Gender: Female; Age: 40; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620781 Subject25_before Human colon biopsies before intervention Subject number: Subject25; Disease status: IBD; Gender: Male; Age: 51; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620782 Subject26_before Human colon biopsies before intervention Subject number: Subject26; Disease status: IBD; Gender: Female; Age: 54; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620783 Subject27_before Human colon biopsies before intervention Subject number: Subject27; Disease status: IBD; Gender: Male; Age: 40; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620784 Subject27_after Human colon biopsies after intervention Subject number: Subject27; Disease status: IBD; Gender: Male; Age: 40; Intervention status: After Case marker detected.
Inflammatory bowel disease Case GSM620787 Subject29_before Human colon biopsies before intervention Subject number: Subject29; Disease status: IBD; Gender: Male; Age: 47; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620788 Subject30_before Human colon biopsies before intervention Subject number: Subject30; Disease status: IBD; Gender: Male; Age: 54; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620792 Subject33_before Human colon biopsies before intervention Subject number: Subject33; Disease status: IBD; Gender: Male; Age: 46; Intervention status: Before Case marker detected.
Inflammatory bowel disease Case GSM620793 Subject56_before Human colon biopsies before intervention Subject number: Subject56; Disease status: IBD; Gender: Male; Age: 55; Intervention status: Before Case marker detected.
Unassigned Unassigned GSM620752 Subject3_before Human colon biopsies before intervention Subject number: Subject3; Disease status: IBS; Gender: Female; Age: 65; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620753 Subject3_after Human colon biopsies after intervention Subject number: Subject3; Disease status: IBS; Gender: Female; Age: 65; Intervention status: After No explicit case or control marker detected.
Unassigned Unassigned GSM620754 Subject4_before Human colon biopsies before intervention Subject number: Subject4; Disease status: IBS; Gender: Male; Age: 44; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620758 Subject7_before Human colon biopsies before intervention Subject number: Subject7; Disease status: IBS; Gender: Male; Age: 57; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620759 Subject7_after Human colon biopsies after intervention Subject number: Subject7; Disease status: IBS; Gender: Male; Age: 57; Intervention status: After No explicit case or control marker detected.
Unassigned Unassigned GSM620760 Subject8_before Human colon biopsies before intervention Subject number: Subject8; Disease status: IBS; Gender: Female; Age: 25; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620761 Subject8_after Human colon biopsies after intervention Subject number: Subject8; Disease status: IBS; Gender: Female; Age: 25; Intervention status: After No explicit case or control marker detected.
Unassigned Unassigned GSM620769 Subject14_before Human colon biopsies before intervention Subject number: Subject14; Disease status: IBS; Gender: Female; Age: 63; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620772 Subject17_before Human colon biopsies before intervention Subject number: Subject17; Disease status: IBS; Gender: Male; Age: 61; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620773 Subject17_after Human colon biopsies after intervention Subject number: Subject17; Disease status: IBS; Gender: Male; Age: 61; Intervention status: After No explicit case or control marker detected.
Unassigned Unassigned GSM620774 Subject18_before Human colon biopsies before intervention Subject number: Subject18; Disease status: IBS; Gender: Female; Age: 39; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620775 Subject19_before Human colon biopsies before intervention Subject number: Subject19; Disease status: IBS; Gender: Male; Age: 65; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620777 Subject21_before Human colon biopsies before intervention Subject number: Subject21; Disease status: IBS; Gender: Male; Age: 69; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620778 Subject22_before Human colon biopsies before intervention Subject number: Subject22; Disease status: IBS; Gender: Female; Age: 65; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620785 Subject28_before Human colon biopsies before intervention Subject number: Subject28; Disease status: IBS; Gender: Male; Age: 64; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620786 Subject28_after Human colon biopsies after intervention Subject number: Subject28; Disease status: IBS; Gender: Male; Age: 64; Intervention status: After No explicit case or control marker detected.
Unassigned Unassigned GSM620789 Subject31_before Human colon biopsies before intervention Subject number: Subject31; Disease status: IBS; Gender: Female; Age: 58; Intervention status: Before No explicit case or control marker detected.
Unassigned Unassigned GSM620790 Subject31_after Human colon biopsies after intervention Subject number: Subject31; Disease status: IBS; Gender: Female; Age: 58; Intervention status: After No explicit case or control marker detected.
Unassigned Unassigned GSM620791 Subject32_before Human colon biopsies before intervention Subject number: Subject32; Disease status: IBS; Gender: Male; Age: 46; Intervention status: Before No explicit case or control 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.