Abstract 716: STAT1 expression in the tumor-stroma microenvironment is influenced by loss of PTEN in prostate cancer
Bibliographic record
Abstract
Abstract The prostate cancer (PCa) microenvironment is an admixture of stromal cells, such as lymphocytes, fibroblasts, myofibroblasts and blood vessel endothelium. The reactive stromal microenvironment of PCa facilitates tumor growth through cytokine and chemokine-mediated cell signaling. STAT1, a transcription factor, induces cell cycle arrest, apoptosis and modulates immune and inflammatory response through IFN-á/ã cytokine activation. IFN-á/ã may be secreted in response to PI3K/AKT activation, since this pathway is associated with JAK/STAT signaling. In addition, the PI3K/AKT pathway can become activated when the PTEN prognostic biomarker is deleted in PCa. The rationale for this project is that the immediate stromal microenvironment of PCa may become pro-tumorigenic as a result of induction of inflammatory cytokines caused by PTEN deletions and activation of PI3K/AKT. We performed FISH analysis of the PTEN gene on 172 cores on a PCa tissue microarray (TMA) derived from 43 patients with intermediate risk disease. Analysis of cytoplasmic and nuclear STAT1 in both the tumor and stromal compartments was performed on each TMA core using immunohistochemistry (IHC) to determine whether the tumor PTEN deletion status was associated with STAT1 expression. In each core, tumor and stromal cell histologies were evaluated independently to estimate the percentage area that was stained positive by IHC. The staining was graded as percentage of positive cells with 0 (negative), 1 (less than 10%), 2 (11% to 50%), and 3 (more than 51%). We found that STAT1 expression in stroma was increased when the PTEN gene in the adjacent tumor was homozygously deleted (p = 0,04). We also showed that mean STAT1 expression in benign tissue cores was reduced when compared to the average score from tumor tissue with one (p = 0.01) or two copies (p = 0.03) of the PTEN gene. STAT1 expression and PTEN gene copy numberPTEN copy numberMean STAT1 in StromaMean STAT1 in Tumor>2 copies0.410.822 copies0.510.651 copy0.600.700 copies0.850.85 These results suggest that the STAT1 pathway may be influenced by PTEN loss in this tumor, suggesting that the JAK/STAT inflammatory pathway may have future clinical applications in PCa. Citation Format: Thiago Vidotto, Clarissa G. Picanço-Albuquerque, Fabiano P. Saggioro, Rodolfo Borges dos Reis, David Robert Siemens, Madhuri Koti, Jeremy A. Squire. STAT1 expression in the tumor-stroma microenvironment is influenced by loss of PTEN in prostate cancer. [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 716.
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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) | 0.002 | 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".