Abstract 3853: Investigating PRL2/<i>PTP4A2</i> as a new target for glioblastoma treatment
Bibliographic record
Abstract
Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor. The standard treatment consists in tumor resection followed by chemo- and radio- therapy. However, tumor recurrence still remains inevitable, and the average lifespan of patients is only 15 months. Over the past decades, targeted therapies such as anti-angiogenic therapy, were proposed but failed to improve overall survival. In this context, the identification of new therapeutic targets is fundamental to implement current treatments. Protein Tyrosine Phosphatases (PTPs) are known to be involved in oncogenesis in several types of cancer, including GBM. Oncogenic properties of PRL2 has been demonstrated in different tumors (e.g. leukemia, breast, lung and nasopharyngeal cancer), but no evidence of PRL2 involvement in GBM has been reported so far. The aim of this project is to understand the role of PRL2 in GBM development, in order to evaluate the potential of PRL2 inhibition as a new therapeutic strategy. Analysis of TCGA (The Cancer Genome Atlas) dataset revealed that PRL2 was a poor prognostic factor in gliomas, and its expression correlated GBM aggressiveness. PTP4A2 expression also correlated with expression of genes involved in immune responses, reactive oxygen species, actin cytoskeleton and trafficking. Thus, we oriented our work towards these directions. To study PRL2 effects both in brain tumor cells and microenvironment, we used spheroids of patient-derived GBM cells, in which PTP4A2 expression was modulated. In vitro assays showed that migration, invasion and adhesion abilities were increased in PTP4A2-KO cells but cell proliferation was not affected. Next, in orthotopic xenografts experiments, PRL2 over-expression promoted tumor growth and reduced mouse survival rate. In addition, to overcome PRLs functional compensation and to use a clinically relevant strategy, we targeted all PRLs (PRL1, 2 and 3) activity with an inhibitory compound. Inhibiting all PRLs drastically reduced viability of GBM cells. Our project aims at discovering how PRL2 is involved in the progression and tumor microenvironment of GBM. Our results indicate that PRL2 promotes GBM growth in response to microenvironmental pressure and its inhibition improves mouse outcomes. However, the precise mechanisms of this regulation are still under investigation. Targeting PRLs and particularly PRL2 open avenue for therapeutic strategy in GBM treatment. Citation Format: Tiffanie Chouleur, Marie-Alix Derieppe, Wilfried Souleyreau, Michel L. Tremblay, Andreas Bikfalvi. Investigating PRL2/PTP4A2 as a new target for glioblastoma treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3853.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".