Abstract 1977: The protein phosphatase 2 subunit PR48 is a novel melanoma tumor suppressor gene.
Bibliographic record
Abstract
Abstract Cutaneous melanoma cell proliferation is a strong prognostic factor for distant metastasis free survival (DMFS). In the current study we tested if aberrant expression of a regulator both DNA replication and cell cycle progression, i.e. the protein phosphatase 2A subunit PR48, could be a driver of melanoma proliferation and progression. Quantitative analysis of PR48 mRNA expression revealed a strong correlation between low levels of expression and poor DMFS in a multivariate analysis (n=49, p=0.0007). In line with this, no or low PR48 protein expression was associated with poor overall survival in three independent samples sets of melanoma (n=339, P<0.001), and reduced PR48 expression correlated with increased proliferation (P=0.0023). Functional analysis using over expression and knock down strategies in melanoma cell lines demonstrated that PR48 alters cdc6-cdt1 complex formation, regulates pRb phosphorylation status, and entry into the S-phase of the cycle progression. Ectopic PR48 expression decreased tumorigenicity of melanoma cells, and shRNA-mediated reduced PR48 expression increased tumor take and growth in nude mice. Our data demonstrate that PPP2R3B is a novel tumor suppressor gene in melanoma, whose loss of expression contributes increased proliferation and poor survival. Citation Format: Léon CL van Kempen, Jonathan Jarry, Mounib Elchebly, Margaret Redpath, Per-Henrík Edqvist, Fredrik Pontén, Richard Scolyer, Dirk Schadendorf, Celia M.T. Greenwood, Joost van den Oord, Alan Spatz. The protein phosphatase 2 subunit PR48 is a novel melanoma tumor suppressor gene. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1977. doi:10.1158/1538-7445.AM2013-1977
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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 | 0.000 | 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) | 0.006 | 0.003 |
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".