Primary testicular lymphoma demonstrates an over-expression of Wilms tumor 1 gene and different mRNA and miRNA expression profiles compared to nodal diffuse large B-cell lymphoma
Bibliographic record
Abstract
Abstract Diffuse large B-cell lymphoma (DLBCL) shows a high degree of clinical and biological heterogeneity. Primary testicular lymphoma (PTL) is an extra nodal variant of DLBCL associated with higher risk of recurrence including contralateral testicle and central nervous system sanctuary sites. Several molecular aberrations including somatic mutation of MyD88, CD79B and upregulation of NF-Kb, PDL-1 and PDL-2 are thought to contribute to the pathogenesis and poor prognosis of PTL. However, additional biomarkers are needed that may improve the prognosis and help understand the PTL biology and possibly lead to new therapeutic targets. RNA from diagnostic tissue biopsies of PTL (n=31) and matched nodal DLBCLs (n=27) patients, were evaluated by mRNA and miRNA expression. Expression of 770 key genes were screened, utilizing nCounter Human miRNA and PAN-cancer pathway mRNA assays utilizing nCounter analysis System (Nanostring technologies). PTL and nodal DLBCL patients were comparable in age, gender, stage, and putative cell of origin (P>0.05). WT1 expression was higher in PTL compared to nodal DLBCL (> 3-fold; P= 0.0001). In addition, we found that WT1 associated pathway genes THBS4, PTPN5, PLA2G2A and IFNA17 were upregulated in PTL (>2.0-fold, P<0.005). The miRNAs targeting WT1 (hsa15a-5p, hsa-miR-16-5p, hsa-miR-361-5p, hsa-miR-27b-3p, hsa-miR-199a-5p, hsa-miR-199b-5p, hsa-miR-132-3p, hsa-miR-128-3p) were upregulated in PTL compared to nodal DLBCL (≥2.0-fold; FDR 0.01). We also found lower expression of BMP7, LAMB3, GAS1, MMP7 and LAMC2 (>2.0- fold, P<0.01) in PTL compared to nodal DLBCL. Our study demonstrated an overexpression of WT1 in PTL compared to nodal DLBCL. We hypothesize that a select miRNA subset targets the WT1 expression and influences the PI3k/Akt pathway in PTL. Additional studies are needed to further investigate the biological role of WT1 in PTL and its potential as a therapeutic target.
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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 | 0.000 |
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".