Abstract A34: Id-1 mediates glioma stem cell chemoresistance to temozolomide
Bibliographic record
Abstract
Abstract Introduction: Id-1 (inhibitor of differentiation and DNA binding) is a transcriptional regulator involved in stem cell maintenance. It has previously been shown to regulate self-renewal and confer chemoresistance in colon cancer stem cells. Id-1 has not been studied within the context of glioblastoma (GBM). We hypothesized that Id-1 mediates glioma stem cell (GSC) survival in response to chemotherapy and subsequently promotes tumour recurrence. Methods: To study the role of Id-1 in response to chemotherapy in vitro, three GSC lines were treated with the chemotherapy agent, temozolomide (TMZ), for seven days. Immunoblot and comparative QT-PCR were used to measure Id-1 protein and mRNA expression post-TMZ, respectively. To evaluate Id-1 expression in patient samples, we constructed a tissue microarray (TMA), which included 77 tissue specimens from patients diagnosed with GBM. Detailed clinical information was available for all of the selected samples, including survival times, treatment regimens, and primary versus recurrent tumor status. Immunohistochemistry was performed on the TMA and Id-1 protein expression was subsequently quantified using Panoramic Image Analysis Software Platform. Id-1 expression was correlated to survival outcome, along with other clinically relevant variables. We also employed a bioinformatics approach, exploring survival data from The Cancer Genome Atlas (TCGA) database that were based on Id-1 expression for patients diagnosed with GBM. Results: Id-1 expression in GSCs strongly increased in response to increasing doses of TMZ in vitro (0 uM, 25 uM, 100 uM). In patient tumor samples (n=77), Id-1 expression did not correlate with survival. However, among the recurrent patients who received chemotherapy after primary tumor resection (n=6), patients with increased Id-1 expression post-chemotherapy had a shorter latency to recurrence compared to patients with decreased Id-1 expression post-chemotherapy. Finally, the TCGA data corroborated our TMA patient data, finding comparable overall survival trends between patients with high versus low Id-1 expression. Conclusion: These findings demonstrate that Id-1 levels increase in response to chemotherapy, suggesting its potential role in chemoresistance. Since resistance to chemotherapeutic drugs is one of the major reasons for treatment failure in glioblastoma, Id-1 inactivation may serve as a novel strategy for enhancing therapy and improving outcomes in patients with the disease. Citation Format: Angela Celebre, Megan YiJun Wu, Marc Remke, Michael Taylor, Jason Karamchandani, Sunit Das. Id-1 mediates glioma stem cell chemoresistance to temozolomide. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A34.
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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) | 0.003 | 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".