Expression of CD133 and poor outcome in neuroblastoma associated with chemoresistance mediated by AKT pathway
Bibliographic record
Abstract
10007 Background: Neuroblastoma is a frequent childhood cancer with very heterogeneous prognosis. Recent studies showed that CD133 expression is an independent prognostic marker for low survival in several cancers like medulloblastoma. The aim of our study is to determine the prognostic value of CD133 expression in a large population of neuroblastoma and to determine the chemoresistance of neuroblasts expressing CD133. Methods: 280 tumor samples of neuroblastoma were screened for CD133 expression. Patients had a median follow-up of 7.15 years. One hundred eighteen patients were under one year of age with a median age of 27 months. There were 67 stage 1, 46 stage 2, 43 stage 3, 99 stage 4, and 25 stage 4S. The association of CD133 expression with relapse and survival were determined through univariate and multivariate analysis. Sensitivity of purified CD133+ neuroblasts isolated from 2 human neuroblastoma cell lines (SKNSH and NB10) to doxorubicin, vincristine and cisplatin was evaluated in vitro, as single agents or in combination with LY294002, a AKT inhibitor. Results: CD133 was expressed in 95 of 280 tumors (33%). There was a significant association between CD133 expression and the following poor prognosis co-variates: age (p<0.0001), INSS stage (p<0.0001), MYCN amplification (p<0.0001). Patients with a CD133+ tumor had a three year event-free and overall survival of 43±5% and 51±5%, respectively, as compared to patients with a CD133- tumor with 88±2% (P<0.001) and 95±2% (p<0.001). In a multivariate model, CD133 expression was independently associated with a decreased overall survival (p = 0.003) in the entire cohort. In vitro purified CD133+ neuroblasts were significantly resistant to chemotherapy as compared to their CD133- cells counterpart, but not in presence of the AKT inhibitor. In vitro treatment of unsorted neuroblasts with the three anticancer drugs significantly enriched the CD133+ subpopulation but not in presence of the AKT inhibitor. CD133plus; significantly expressed higher levels of activated proteins in the AKT pathway than CD133−. Conclusions: CD133 is independently associated with a worse outcome in patents with neuroblastoma. This prognosis factor is associated with in vitro resistance to chemotherapy involving activation of the AKT pathway. No significant financial relationships to disclose.
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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 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".