Abstract LB-332: High-throughput proteomic analysis identifies protein S as a potential modulator of androgen-independent prostate cancer
Bibliographic record
Abstract
Abstract Prostate cancer is the most commonly diagnosed and second leading cause of death due to cancer in men. Androgen deprivation remains the mainstay therapy, which is efficient in shrinking androgen-dependent tumors. However, many men eventually stop responding to this treatment, progressing to a more lethal androgen-independent prostate cancer. The mechanisms mediating these transitions remain unknown, and as a result, there are no effective treatments. We hypothesize the presence of specific modulators, important for the progression to androgen-independency. To test this, we performed high-throughput proteomic analysis on the conditioned media of the androgen-dependent cell lines LNCaP and VCaP, androgen-independent cell lines LNCaP-SF, DU-145, PC3, PPC1, 22Rv1, as well as a normal prostate cell line (RWPE). This allowed us to compile a comprehensive data set, permitting us to mine for differentially secreted proteins that could serve as potential markers for androgen-independent cancers. We utilized quantitative real-time PCR, as well as in vitro wound healing assays to corroborate our proteomic analysis results. We were able to identify the anti-coagulant factor, Protein S (PROS1), as a potential modulator and marker of androgen-independence. Based on spectral counts, PROS1 was found highly secreted in all the androgen-independent cell lines, with no detectable secretion in the normal or androgen-dependent cell lines. The gene expression profile of the androgen-independent cell lines also maintained the over-expression of PROS1, when compared to the normal and androgen-dependent cell lines, while only prostate cancer tissue samples showed an upregulation of PROS1. Furthermore, recombinant PROS1-treated LNCaP cells demonstrated an increase in wound repair and invasive growth potential, implying that PROS1 may have functional roles outside of the coagulation pathway. Our results suggest that PROS1 is involved in the progression of androgen-independent prostate cancers. 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 LB-332. doi:10.1158/1538-7445.AM2011-LB-332
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.012 | 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 teacher head, 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".