Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer
Bibliographic record
Abstract
Metastatic colon cancer remains incurable despite improvements in survival outcomes. New therapies based on the discovery of colon cancer genomic subsets could improve outcomes. Colon cancers from genomic studies with publicly available data were examined to define the expression and regulation of the major tight junction proteins claudins and occludin in genomic groups. Putative regulations of the promoters of tight junction genes by colon-cancer-deregulated pathways were evaluated in silico. The effect of claudin mRNA expression levels on survival of colon cancer patients was examined. Common mutations in colon-cancer-related genes showed variable prevalence in genomically identified groups. Claudin genes were rarely mutated in colon cancer patients. Genomically identified groups of colon cancer displayed distinct regulation of claudins and occludin at the mRNA level. Claudin gene promoters possessed clustered sites of binding sequences for transcription factors TCF4 and SMADs, consistent with a key regulatory role of the WNT and TGFβ pathways in their expression. Although an effect of claudin mRNA expression on survival of colon cancer patients as a whole was not prominent, survival of genomic subsets was significantly influenced by claudin mRNA expression. mRNA expression of the main tight junction genes showed differential regulation in various genomically defined subgroups of colon cancer. These data pinpoint a distinct role of claudins and pathways that regulate them in these subgroups and suggest that subgroups of colon cancer should be considered in future efforts to therapeutically target claudins.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".