Abstract 5914: E-cadherin and beta-catenin in oral dysplasia progression
Bibliographic record
Abstract
Abstract Objectives: Epithelial-mesenchymal transition (EMT), a biological process characterized by a progressive decrease in epithelial features and increase in mesenchymal traits, has been suggested as a critical mechanism in cancer development. A defining feature of EMT is the loss of E-cadherin. Together with beta-catenin, alpha-catenin, and p120-catenin, E-cadherin forms the adherens junctions, which are involved in cell-cell adhesion of epithelial cells. As beta-catenin has both a structural and signaling role, E-cadherin potentially contributes to malignant progression via beta-catenin signaling through the Wnt pathway. E-cadherin and beta-catenin expression is altered from normal oral tissue, oral epithelial dysplasia (OED), to oral squamous cell carcinoma (OSCC), but there is no longitudinal research on the role of these biomarkers in malignant progression. The objective of this study is to explore the expression of E-cadherin and beta-catenin in OED and to determine if these expression patterns predict malignant progression. Methods: 28 progressors (PR) and 56 non-progressors (NPR) were included in this case-control study. Samples that progressed to severe OED, carcinoma in situ, or OSCC were categorized as PRs, and samples that did not progress were NPRs. Patient samples with a baseline biopsy of low-grade (mild or moderate) OED and at least 5 years of follow-up for NPRs were obtained from the Oral Cancer Prediction Longitudinal study, which has been prospectively following patients with OED for over 20 years. Immunohistochemistry (IHC) is performed on formalin-fixed paraffin-embedded tissue samples to assess for reduced membranous E-cadherin, and reduced membranous and increased cytoplasmic and/or nuclear beta-catenin expression in PRs compared to NPRs. We hypothesized that OED with this expression pattern will show greater likelihood of progression. Fisher’s exact test was used. Logistic regression will be performed to predict progression. Results: There were no significant differences in age, sex, risk of lesion site, and grade of dysplasia between PRs and NPRs. There were significant differences in length of follow-up time and smoking history. IHC has been completed on 27 samples to date, which show decreased membranous beta-catenin expression in PRs compared to NPRs (p=0.042). IHC for additional samples will be performed to assess for cytoplasmic and nuclear beta-catenin expression, and to compare expression patterns between PRs and NPRs to determine prediction of malignant progression. Conclusion: Early results suggest that membranous beta-catenin expression may be decreased in OED that progressed compared to OED that did not. This research enhances the understanding of EMT’s role in malignant progression and hopes to potentially aid in the intervention of oral lesions at risk of cancer. Citation Format: Ilena Yim, Iris Lin, Leigha Rock, Lewei Zhang, Miriam Rosin, Denise Laronde. E-cadherin and beta-catenin in oral dysplasia progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5914.
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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) | 0.004 | 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".