Molecular profiling of TOX-deficient neoplastic cells in cutaneous T cell lymphoma
Bibliographic record
Abstract
Cutaneous T cell lymphoma (CTCL) is a rare but potentially devastating primary cutaneous lymphoma. CTCL is characterized by localization of neoplastic T lymphocytes to the skin, with mycosis fungoides (MF) and its leukemic form, Sézary syndrome (SS) being the most common variants. Thymocyte selection-associated high-mobility group box (TOX) gene has been found to be highly expressed in MF and SS. It is reported that higher expression levels of TOX in patients will increase risks of disease progression and poor prognosis. However, the molecular events leading to these abnormalities have not been well understood. To better understand the molecular mechanism underlying TOX-mediated differentially expressed genes (DEGs) in CTCL, and to identify DEGs pathways triggered after knockdown of TOX gene in the CTCL cell line Hut78, we employed two shRNA-mediated lentiviruses to knock down TOX gene in the skin lymphoma cell line HuT78. RNA sequencing (RNAseq) analysis was applied to analyze DEGs, DEGs GO and their corresponding pathways. Knockdown of TOX can induce upregulation of 547 genes and downregulation of 649 genes, respectively. HOXC9 was the most significant downregulated gene. Most DEGs are enriched in malignancies and relate to the Wnt and mTOR signaling pathways, and therefore they can regulate cellular processes and induce different biological regulation. Transcriptome analysis of DEGs after knockdown of TOX in our study provides insights into the mechanism of TOX in CTCL and suggests candidate targets for therapy of CTCL.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".