Gene methylation and silencing of <i><scp>SOCS</scp>3</i> in mantle cell lymphoma
Bibliographic record
Abstract
The significance of loss of SOCS3, a negative regulator of signalling pathways including those of STAT3 and NF-κB, was examined in mantle cell lymphoma (MCL). The protein expression and gene methylation status of SOCS3 were detected using immunohistochemistry/Western blots and methylation-specific polymerase chain reaction, respectively. To evaluate its functional importance, SOCS3 was restored in two SOCS3-negative MCL cell lines using a lentiviral vector. Loss of SOCS3 protein expression was found in 3/4 MCL cell lines and 18/33 (54.5%) tumours. SOCS3 was found consistently methylated in cell lines (3/4) and tumours (7/7) negative for SOCS3, and was unmethylated in all SOCS3-positive cell line (1/1) and tumours (5/5) examined. Treatment of all three SOCS3-negative cell lines with 2'-deoxy-5-azacytidine restored SOCS3 expression. SOCS3 is biologically important in MCL, as lentiviral transfer of SOCS3 in SOCS3-negative cell lines increased their apoptotic activity, downregulated nuclear factor (NF)-κB-p65, cyclin D1 (CCND1), BCL2 and BCL-XL (BCL2L1), and substantially dampened interleukin 10-induced STAT3 activation. In 19 patients aged ≤ 69 years at time of diagnosis, we found that those that carried SOCS3-negative tumours showed a trend toward a worse outcome (P = 0.1, log-rank).
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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) | 0.001 | 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".