Expression of mTOR in diffuse large B-cell lymphoma.
Bibliographic record
Abstract
e18535 Background: The mammalian target of rapamycin (mTOR) pathway mediates protein synthesis, cell growth and survival of normal and malignant cells. This pathway is constitutively activated in several B-cell lymphomas. We studied immunohistochemical expression of mTOR, phosphorylated mTOR (pmTOR) and bcl-2 in 55 cases of diffuse large B-cell lymphomas (DLBCL) and their association with established prognostic factors as well as treatment outcomes in a retrospective single instituition study. Methods: After IRB review, 55 cases of DLBCL were identified. Immunostains for mTOR, pmTOR and bcl-2 were performed and their expression correlated with clinical and survival data. Associations of demographic (age and gender), clinical (stage, IPI score) and chemotherapy (RCHOP or other) with marker expression as well as association with recurrence and survival were studied using chi square and t-test for univariate analysis and logistic regression for multivariate evaluation. Results: Of the 55 patients, 44% were > age 65, 65% were males and 65% had advanced stage (III or IV) disease. High IPI scores were noted in 42% and 87% received the RCHOP regimen.On univariate analysis, high mTOR expression was associated with male gender (85% vs. 46%, p<0.01), high IPI score (67% vs. 18%, p, 0.001) and higher mean age (66 vs. 53 years, p < 0.001). With high mTOR expression a trend towards higher stage ( 78% vs 54% p=0.08) and likelihood of poor overall survival (defined as survival <3 years; 41% vs 18% p =0.08) was noted. Further, on univariate analysis bcl-2 expression was associated with higher risk of recurrence (35% vs.11%, p 0.05) whereas no association with clinical factors or outcomes was noted with pMTOR expression. On multivariate analysis the only parameter found to be significant was IPI [0R 11.6 95% CI 1.4-100]. Conclusions: High mTOR expression is associated with gender, age, IPI and showed a trend towards advanced stage and shorter survival. This target needs to be investigated prospectively in DLBCL as a prognostic factor and predictive marker. Given the availability of several mTOR inhibitors, the natural history of patients with poor risk DLBCL(high IPI) with high expression of mTOR may be favorably altered.
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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 | 0.001 | 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".