Up-regulation of SERPINA3 correlates with high mortality of melanoma patients and increased migration and invasion of cancer cells
Bibliographic record
Abstract
// Jiaying Zhou 1, * , Yabin Cheng 2, 3, * , Liren Tang 4 , Magdalena Martinka 5 , Sunil Kalia 3 1 Faculty of Science, University of British Columbia, Vancouver, BC, Canada 2 School of Pharmaceutical Sciences, Xiamen University, Xiamen, China 3 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada 4 Welichem Biotech Inc, Burnaby, BC, Canada 5 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada * These authors have contributed equally to this work Correspondence to: Yabin Cheng, email: chengyb@xmu.edu.cn Sunil Kalia, email: sunil.kalia@vch.ca Keywords: SERPINA3, melanoma, AACT (alpha-1 antichymotrypsin), tissue micro array, cell migration and invasion Received: November 14, 2015 Accepted: March 28, 2016 Published: May 17, 2016 ABSTRACT Serpin Peptidase Inhibitor, clade A member 3 (SERPINA3) was found to be abnormally overexpressed in a subset of melanoma tissue biopsies. High SERPINA3 expression was also associated with poor patient survival. In this study, we set out to test SERPINA3 protein’s prognostic potential with a larger-sized and independent patient cohort, and to explore SERPINA3’s function in melanoma cells. Tissue microarray-based immunohistochemistry analysis showed a significant increase in SERPINA3 expression in invasive and metastatic melanomas compared to normal nevi and melanoma-in-situ ( P < 0.001, Chi-square test). In melanoma patients, high SERPINA3 expression was strongly associated with worse overall and disease specific survival at 5 years. Multivariate Cox regression analysis showed that SERPINA3 expression is an independent prognostic factor to predict melanoma patient clinical outcome. When SERPINA3 expression was selectively silenced using small interfering RNA molecules (siRNA) in cultured melanoma cell lines, cell migration and matrix invasion was significantly decreased, but no change in cell proliferation was observed. This study confirms the prognostic potential of SERPINA3 expression in human cutaneous melanoma and reveals the pro-migration and pro-invasion functions of this protein on melanoma cells.
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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 | 0.001 | 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) | 0.001 | 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".