Association of upregulated GATA-4 transcription factor colorectal adenocarcinoma with metastatic and primary tumors
Bibliographic record
Abstract
e15093 Background: GATA-4 zinc finger transcription factor is involved in regulation of cellular development, proliferation, and differentiation and is important in embryonic development of gastrointestinal tract. However, GATA-4 is not expressed in normal adult colonic mucosa. Its protein expression in colonic adenocarcinoma has not been systematically evaluated and small number of samples was previously reported as negative. Nuclear factor-B (NF-B) activation was shown to promote the growth of the colon tumors in experimental models and was correlated with tumor angiogenesis and progression in human colorectal cancer. Methods: Forty cases of colorectal adenocarcinoma were evaluated. The benign colonic mucosa and the matching metastatic tumors of the same patients were also included in the study. TMAs which included 139 samples were evaluated by immunohistochemistry and nuclear and cytoplasmic GATA-4 expression was scored (0–3+). NF-B activation was detected as nuclear reactivity for p65. Results: GATA-4 was expressed in 32% of colorectal adenocarcinoma, but not in benign colonic mucosa (p=0.0001, Chi-Square). GATA-4 was also significantly more expressed in metastatic (41%) than in primary (21%) colorectal adenocarcinoma (p<0.0001, Chi-Square). NF-B activation was not present in any of the samples of benign colonic mucosa, but it was detected in 64% adenocarcinomas (p<0.0001, Chi-Square). While there was no difference in NF-B activation between primary vs. metastatic adenocarcinoma, a strong positive association between GATA-4 expression and NF-B activation (p<0.0001, Linear-by- Linear) was found. Conclusions: GATA-4, a developmental transcription factor is not expressed by normal colonic mucosa, but is present in 1/5 of primary tumors that gave rise to distant metastases and in almost 1/2 of their respective metastases. GATA- 4 is also strongly positively associated with NF-B activation previously described to have a role in human cancer progression. GATA-4 may have a role in colorectal adenocarcinoma development and progression and it should be further evaluated in prospective studies as a putative adverse prognostic factor in colorectal adenocarcinoma. No significant financial relationships to disclose.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".