Bibliographic record
Abstract
Introduction and Objectives: Mechanisms underlying prostate cancer (Pca) progression from an androgen-responsive to a refractory (castration-resistant) stage prove to be challenging and still poorly understood.Heterogeneity regarding tumor cell sensitivity to androgens may play an important role.Indeed by responding to diverse growth-promoting factors such as interleukin (IL)-6, tumor cells expressing the androgen receptor (AR) may adapt while subsets of AR(-) cells may concomitantly be selected.We identified Fer as the major tyrosine kinase implicated in the IL-6-mediated activation of STAT3 (the signal transducer and activator of transcription) that controls growth of human metastatic Pca cell lines, both AR(+) and AR(-).Moreover, Fer is implicated in cross-talks between IL-6 and AR signaling pathways in AR(+) tumor cells and controls AR-dependent genes.Since Fer is up-regulated in Pca, the aim was to test the hypothesis of an active pathway implicating pairs such as Fer/pSTAT3, Fer/AR, pSTAT3/AR in prostate cancer tissues from patients with advanced disease.Methods: Paraffin-embedded blocks of prostate tissues obtained by TURP from hormone-treated patients (n=29) were retrieved from pathology.Consecutive sections were processed to stain Fer, pSTAT3, and AR by immunohistochemistry. Tumor cell staining was quantified by percentage and intensity and used to calculate H scores. Significance of correlations was analyzed through the Spearman Rho's method.Results: Each TURP case was of good quality for immunohistochemistry.All three markers were primarily found in the nucleus.Overall, 97% (28/29) of cases were AR(+), 86% (25/29) of cases were Fer (+) and 83% (24/29) of cases were pSTAT3(+).A single case was AR(-), while positive for Fer and pSTAT3.Within each case, a majority of tumor cells were AR(+).Yet single cell analysis revealed the tumor heterogeneous nature with respect to AR.Indeed, all specimens contain AR(-) cells, the mean being 17%, interspersed among AR(+) cells.The analysis of pairs of markers revealed no correlation between AR and pSTAT3, and between Fer and AR.Nonetheless, Fer and pSTAT3 were strongly correlated, in both percentages of stained cells (p<0.01) and H score (p<0.0001), and regardless of the tumor cell AR status.In the end, Fer was expressed along with pSTAT3 in both AR(+) and AR(-) cells in 79% of cases.Conclusion: The co-expression of Fer and activated STAT3 in advanced prostate cancer supports that aberrant Fer signaling favors adaptation and selection of tumor cells during progression towards hormone-refractory disease.Supported by Prostate Cancer Canada.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.704 | 0.429 |
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".