Abstract 2654: Immunologic and prognostic correlates of WISP1 in prostate cancer
Bibliographic record
Abstract
Abstract Background: Avoidance of immune destruction and tumor-promoting inflammation are equally important cancer hallmarks. In the context of prostate cancer, inflammatory markers and high levels of immune infiltrates have been associated with shorter biochemical recurrence (BCR)-free survival. WNT1 Inducible Signaling Pathway (WISP1) has been implicated in prostate cancer metastasis and the regulation of inflammation in diverse benign diseases. Thus, the objectives of this study were: 1) to assess the prognostic value of WISP1 in human prostate cancer, and 2) to determine the association of WISP1 to the inflammatory landscape specific to this disease. Methods: A tumor microarray (TMA) was constructed with radical prostatectomy specimens of 285 prostate cancer patients. Multicolor manual immunofluorescence (IF) was performed to simultaneously detect WISP1, CD8 and cytokeratins 8 and 18. WISP1 expression levels were determined by the mean fluorescence intensity (MFI) in stromal, epithelial, cytoplasmic and nuclear (DAPI) areas in each core, and CD8+ cell density was determined for each compartment by dividing cell count by the percentage of the core occupied by the compartment. Finally, the prostate cancer TCGA dataset (n = 548) was used to validate the prognostic value of WISP1 mRNA expression, as well as its association to CD8+ lymphocytes using previously validated gene signatures (Becht et al., 2016). Results: IF analyses of our TMA revealed that high levels of WISP1 in normal adjacent epithelium are significantly associated with shorter BCR-free survival in Kaplan-Meier (log-rank = 4.246, p = 0.039) and univariate Cox regression analyses (hazard ratio = 1.477; p = 0.042), but not in multivariate Cox regression analyses (hazard ratio = 1.381; p = 0.101). Furthermore, a significant correlation was found between WISP1 expression and CD8+ cell density. Gene expression analyses further showed that WISP1-high prostate tumors are associated with a CD8+ lymphocyte gene enrichment profile, and confirmed that patients with WISP1-high prostate tumors have reduced BCR-free survival (Wilcoxon rank, p = 0.003). Conclusions: Overall, our results support a negative prognostic association for WISP1 as well as a proinflammatory role. WISP1 may represent a relevant target for the improvement of prostate cancer immunotherapy. Citation Format: Pierre-Olivier Gaudreau, Sylvie Clairefond, Pierre-Luc Boulay, Pavel Chrobak, Bertrand Allard, Sandra Pommey, Fred Saad, Marian Young, John Stagg. Immunologic and prognostic correlates of WISP1 in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2654.
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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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".