Abstract 4835: Gonosome-linked expression of PPP2R3B in cutaneous melanoma correlates with distant metastasis free survival
Bibliographic record
Abstract
Abstract Background: A strong adverse male effect for melanoma incidence and survival has been reported. No biological explanation, including hormonal differences, has been identified so far. We hypothesize that this gender difference in incidence and survival involves X-linked tumor suppressor genes and/or oncogenes whose expression is affected by X-chromosome alterations. Methods: DNA and RNA were extracted from 49 fresh frozen primary melanomas (32 females, 17 males, distant metastasis free survival (DMFS) <3 years or follow up >3 years) and subjected to array-based comparative genomic hybridization. Supervised and unsupervised cluster analyses were performed. X-inactivation was studied by Xist RNA in situ hybridization and androgen receptor methylation-sensitive PCR. The expression of a candidate X-linked gene was analyzed by quantitative PCR and correlated with DMFS in uni- and multivariate analyses. Results: Supervised cluster analyses revealed distinct DNA signatures associated with clinical and histopathological characteristics. Unsupervised clustering identified three groups of which one was composed of predominantly female patients (10/13) and associated with the worst DMFS. This group was characterized by loss of one X-chromosome in 7 of the 13 patients. Loss of X correlated with poor DMFS of female patients (logrank p=0.009). Intriguingly, the lost X chromosome was systematically the inactivated copy. Among the 17 males, Y-chromosome loss correlated with DMFS (logrank p=0.015). We found that the PPP2R3B gene, located within one of the pseudoautosomal regions and thus not inactivated on the inactive X in females, is lost from the Y in males. PPP2R3B encodes a regulatory subunit of protein phosphatase 2 that may negatively control cell proliferation via targets such as CDC6 or RB. Quantitative analysis of PPP2R3B mRNA expression in an independent sample set of melanomas revealed a strong correlation between decreased levels of PPP2R3B expression and poor DMFS irrespective of gender in multivariate analysis (p=0.0007). Conclusion: Our analyses reveal a specific pattern of X and Y chromosome losses that are associated with melanoma progression. PPP2R3B is a potential gonosome-linked tumor suppressor gene, whose loss of expression correlates with poor DMFS. 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 4835. doi:10.1158/1538-7445.AM2011-4835
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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) | 0.003 | 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".