Abstract 1098: Interactions between P53 and IGF2 in human esophageal adenocarcinoma tissues and cell lines
Bibliographic record
Abstract
Abstract To define the role of the insulin-like growth factor (IGF) axis in esophageal adenocarcinoma (EADC), the objective of this study was to evaluate interactions between IGF2 and P53 in a well characterized series of surgically-resected esophageal tissues and the following cell lines: Het1A (derived from immortalized normal esophageal epithelium), OE33 and JH-EsoAd1 (each derived from a primary EADC). Nucleic acids were extracted from 68 primary EADC (and matched histologically normal) tissues. PCR was performed on gDNA and RT-PCR on RNA followed by ApaI digestion to identify informative (heterozygous) cases and imprinting status, respectively. Expression of IGF2 mRNA was determined by quantitative PCR, and of IGF2 and P53 protein by Western analysis and immunohistochemistry. Molecular findings in tissues were correlated with pathologic and clinical characteristics including patient survival. Functional studies utilizing cell lines evaluated IGF2/P53 interactions. Of 44 informative cases, P53 protein overexpression was significantly higher in normally imprinted tumors (12/30) vs. tumors with loss of IGF2 imprinting (1/14; p<0.05). Multivariable logistic regression confirmed IGF2 imprinting status to be independently associated with P53 expression (OR 0.12, 95% CI 0.01-1.00; p=0.05). Tumors overexpressing both IGF2 and P53 were found to be of advanced stage with poor survival. In patients below age 65 years, IGF2 mRNA expression was significantly higher in tumors with wild type P53, and multivariate analysis showed IGF2 mRNA expression to be independently associated with p53 mutation (OR 0.74, 95% CI 0.58-0.94; p<0.05) and P53 protein expression (OR 0.83, 95% CI 0.69-1.00; p<0.05). Whereas treatment of Het1A cells with IGF2 significantly increased P53 expression (1.34+/-0.06 vs. 1.00+/-0.00 untreated cells; p=0.003), IGF2 did not modulate P53 expression in either of the two tumor cell lines (OE33 and JH-EsoAd1). IGF1 Receptor (IGF1R) inhibition with AG1024 reduced P53 expression only in OE33 (0.48+/-0.22 vs. 1.00+/-0.00 untreated cells; p=0.05) and JH-EsoAd1 (0.71 +/- 0.23 vs. 1.00+/- 0.00 untreated; p = 0.15) cells, an effect not reversed by IGF2 treatment. In conclusion: 1) these studies identify novel molecular regulatory interactions between P53 and IGF2 in esophageal malignancy, which are dependent on IGF2 imprinting status and tissue/cell type. 2) Overexpression of both IGF2 and P53 in esophageal tumors is associated with aggressive disease in younger patients (below age 65 years), and may represent clinically useful biomarkers to define a biologically distinct subset of EADC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1098. doi:10.1158/1538-7445.AM2011-1098
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".