Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma
Bibliographic record
Abstract
BACKGROUND: Krüppel-type zinc finger protein genes located on chromosome 19q13 are aberrantly hypermethylated with high frequency in all anatomic sub-sites of head and neck cancers as well as other epithelial tumours resulting in decreased expression. METHODS: We examined prognostic significance of ZNF154 and ZNF132 expression and DNA methylation in independent patient cohort of about 500 head and neck cancer patients in the Cancer Genome Atlas (TCGA). We also overexpressed these genes in HEK-293 cells, as well as the oral cancer cell line UM-SCC-1. RESULTS: In 20 patients from the TCGA cohort of HNSCC patients where ZNF154 and ZNF132 DNA methylation and RNA expression could be compared in tumor and adjacent normal tissue, there was increased DNA methylation and decreased expression of both ZNF154 and ZNF132 in primary tumours. Low ZNF154 and low ZNF132 expression were associated with shorter overall survival in both head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAC patients). While expression of these proteins in HEK-293 cells produced full-length protein, only truncated copies could be expressed in head and neck cancer cells (UM-SCC-1). The truncated version of ZNF154 protein increased doubling time and reduced cell migration in UM-SCC-1 cancer cells. CONCLUSIONS: Both ZNF132 and ZNF154 represent novel clinically significant biomarkers in head and neck cancer with potential tumour suppressive properties. Future studies will address the underlying molecular mechanisms by which ZNF154 expression in HNSCC contributes to the control of cell growth and migration.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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".