flowchart TD
A["Eligibility + consent"] --> B{"Study group"}
B -->|High-risk UC| C["Plasma + colonic tissue"]
B -->|CRC comparator| D["Plasma + colonic tissue"]
B -->|Healthy comparator| E["Plasma + colonic tissue"]
C --> M["DNA extraction + methylation profiling"]
D --> M
E --> M
C --> S["Serum sIgA by ELISA"]
M --> Q["Quality control + differential methylation"]
S --> Q
Q --> A2["Association with inflammation + phenotype"]
A2 --> V["Candidate integrated signature"]
V --> R["Independent validation required"]
Study design
Research question, objectives, cohorts, specimens, and analytical plan
The central question
Can differential methylation signatures in plasma cell-free DNA and colonic tissue, interpreted together with serum sIgA and inflammation markers, help characterize ulcerative colitis patients at high risk of colorectal cancer progression?
Why this matters
Read the clinical-context Field Note: from ulcerative colitis to colorectal cancer →
Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa. In long-standing or extensive disease, repeated injury and repair can contribute to dysplasia and colitis-associated colorectal cancer (CRC). Colonoscopic surveillance remains central to care. This project explores a complementary molecular layer: epigenetic state through DNA methylation and mucosal immune state through sIgA.
The goal is not to replace colonoscopy. It is to investigate whether less-invasive blood-derived measurements, anchored to colonic tissue and clinical context, can contribute to future risk-stratification strategies.
Epigenetic–immune hypothesis
The team hypothesizes that aberrant DNA methylation—potentially including hypermethylation near genes involved in mucosal immune regulation—may be associated with altered sIgA biology, persistent inflammation, and progression-related phenotypes. This is a directional biological model to test, not an established causal chain: methylation may be cause, consequence, cell-composition marker, or correlate of inflammation, and sIgA regulation is not controlled by a single epigenetic switch.
Objectives
- Characterize DNA methylation profiles in plasma cell-free DNA and colonic biopsies from patients with high-risk UC.
- Compare those profiles with healthy and CRC comparator groups.
- Test associations between serum sIgA and methylation signatures identified in liquid biopsy and colonic tissue.
- Examine relationships among methylation, sIgA, and inflammatory markers in high-risk UC.
Planned design
The clarified design is a descriptive, cross-sectional study with an analytical component: 18 participants contribute paired plasma and colonic-tissue specimens, producing 36 planned specimens.
| Group | Participants | Plasma cfDNA | Paired colonic tissue | Role |
|---|---|---|---|---|
| Ulcerative colitis | 8 | 8 | 8 | High-risk disease group |
| Colorectal cancer | 5 | 5 | 5 | Neoplastic comparator |
| Healthy comparators | 5 | 5 | 5 | Reference group |
| Total | 18 | 18 | 18 | 36 specimens |
NotePairing clarified
The research team describes plasma and tissue as paired within each of 18 participants. The table is a planned design and does not imply that recruitment, processing, or analysis is complete.
From sample to interpretation
Eligibility described for the UC group
- Confirmed UC with more than eight years of disease or primary sclerosing cholangitis.
- Exclusion of Crohn’s disease, contraindication to colonoscopy or biopsy, and prior colonic surgery, as described in the slides.
- Recruitment sites named in the presentation include Cobos Medical Center, HIC Bucaramanga, and GastroAdvanced.
Analysis frame
The source presentation proposes descriptive summaries for continuous and categorical variables, followed by association testing using chi-square or Fisher’s exact tests as appropriate, with a 95% confidence level and a nominal threshold of p ≤ 0.05.
For biomarker development, that plan is a starting point. A robust downstream workflow should also pre-specify methylation quality control, cell-composition and batch adjustment, multiple-testing correction, effect sizes with confidence intervals, missing-data handling, and an independent validation strategy.
Ethics and responsible data use
The presentation identifies Colombian Resolution 8430 of 1993, informed consent, and approval by the HIC Bucaramanga–Fundación Cardiovascular de Bucaramanga research committee (Minutes 005-2024). Public GitHub content must remain de-identified and contain no participant-level clinical, genomic, or other sensitive data.
WarningResearch, not medical advice
This is an exploratory biomarker study. No methylation or sIgA result described here is validated for diagnosing UC, predicting cancer, or directing an individual’s care.