Abstract 5031: Melanoma progression involves a profound nuclear to cytoplasmic shift of the transcription factor SUM-6 (specifically upregulated in melanoma gene six)
Bibliographic record
Abstract
Abstract INTRODUCTION: SUM-6 is a human homeobox gene that encodes for a transcription factor, which plays a key role in normal embryogenesis. Overexpression of both the gene and nuclear protein has been shown to occur in a variety of cancers such as breast, colorectal, and pancreatic, and has been demonstrated to promote tumorigenesis. The purpose of the current study was to evaluate the expression of the SUM-6 protein, its clinical relevance, and biological function in melanoma. EXPERIMENTAL PROCEDURES: Immunohistochemistry using a specific SUM-6 antibody was performed on a tissue microarray consisting of 438 patient biopsies, which included benign and malignant melanocytic tumors. Double-blinded scoring of distinct nuclear and cytoplasmic SUM-6 staining was performed. SPSS 16.0 statistical package and Microsoft Excel were used to carry out the analyses of data. Analyses included the χ2 test and univariate analysis by the log-rank test in conjunction with the Kaplan-Meier survival curve for visualization. RESULTS: Nuclear staining of SUM-6 was detected in 100% of normal nevi (n = 19), 81% of dysplastic nevi (n = 32), 87% of melanoma in situ (n = 23), 79% of primary melanoma (n = 219), and 53% of metastatic melanoma (n = 145), whereas cytoplasmic staining was detected in 63%, 94%, 56%, 94%, and 97%, respectively. Univariate analysis revealed that five year disease-specific survival decreased significantly when SUM-6 was excluded from the nucleus and when SUM-6 levels were elevated in the cytoplasm (p = 0.001 and 0.019, respectively). CONCLUSIONS: We concluded that melanoma progression and metastasis is associated with a profound shift of transcription factor SUM-6 from the nucleus to the cytoplasm. It is interesting to note that in most other cancers, the SUM-6 protein was instead overexpressed in the nucleus. The patients in whom SUM-6 was excluded from the nucleus demonstrated a significantly worse prognosis than the patients who retained nuclear expression. These findings suggest that either the absence of nuclear expression or elevated cytoplasmic presence (or both) of SUM-6 may play a role in the progression of malignant melanoma. Citation Format: Laura J. Graziano, Xue Zhang, Yabin Cheng, Gang Wang, Mingwan Su, Magdalena Martinka, Youwen Zhou. Melanoma progression involves a profound nuclear to cytoplasmic shift of the transcription factor SUM-6 (specifically upregulated in melanoma gene six). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5031.
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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) | 0.007 | 0.002 |
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".