Abstract 4102: p27 as a biomarker and determinant of risk for endometrial carcinoma arising in the setting of obesity
Bibliographic record
Abstract
Abstract Endometrial carcinoma exhibits the strongest association with obesity of any cancer. Tumor growth is driven by PI3K/AKT activation, and opposed by tumor suppressors, including the tuberous sclerosis complex (TSC) and p27, with inactivation of TSC2 and loss of cytoplasmic misloclization of p27 both being linked to PI3K/AKT signaling. However, little is known about the involvement of p27 in the development of endometrial carcinoma arising in the setting of obesity, expecially its role in early disease progression. We found that p27 was moderatley-to-severely reduced in both “normal” endometrial glands as well as endometrial hyperplasia of obese women. Obese Tsc-2-deficient Eker rats similarly developed endometrial hyperplasia with a high frequency and short latency, and like obese women, endometrial hyperplasia that developed in obese rats exhibited loss of p27. In Eker rats, even a short duration of caloric restriction (2-4 months of age) reduced weight, increased adiponectin and lowered leptin to produce favorable leptin:adiponectin ratio, and reduced circulating insulin levels. Caloric restriction also increased p27 levels, primarily in the nucleus, and significantly decreased endometrial hyperplasia incidence by up to 50%. These data demonstrate that in the setting of obesity, loss of p27 occurs very early in progression to carcinoma. Importantly, p27 can be modulated along with weight by diet, and perhaps other lifestyle interventions that decrease risk for development of carcinoma, suggesting it may be a useful biomarker, and possible determinant of risk for endometrial carcinoma in the setting of obesity. Citation Format: Adrienne S. McCampbell, Megan L. Mittlestedt, Ruhee Dere, Lijun Zhou, Bojana Djordjevic, Pamela T. Soliman, Qian Zhang, Caimiao Wei, Stephen D. Hursting, Karen H. Lu, Cheryl L. Walker, Russell R. Broaddus. p27 as a biomarker and determinant of risk for endometrial carcinoma arising in the setting of obesity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4102. doi:10.1158/1538-7445.AM2014-4102
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.003 | 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".