Expression Profile of Thymidine Kinase Genes in Cervical Squamous Cell Carcinoma Confirmed by Various Detection Methods
Bibliographic record
Abstract
Background: Thymidine kinases (TKs) are key enzymes involved in DNA synthesis and repair, with alterations in their expression associated with various cancers. Thymidine kinase 1 (TK1) and TK2 are cytosolic enzyme proteins that catalyze the addition of a gamma-phosphate group to thymidine. The existing literature on TK1 in cervical squamous cell carcinoma (CESC) fails to address the clinical role of TK1 overexpression and its possible molecular mechanism in CESC. The clinical significance of TK2 in CESC is also unknown. The objective was to explore the differential expression, clinical significance, and molecular mechanisms of TK1 and TK2 in CESC. Methods: The researchers collected global high-throughput data, extracted the expression levels of TK1 and TK2, and calculated the integrated standardized mean difference (SMD) and summarized receiver’s operating characteristics (sROC) of TK1 or TK2 mRNA to investigate the expression profiles of TK genes fully and objectively in 918 CESC tissues and 360 control tissues. In-house tissue microarrays for immunohistochemical testing were used to verify the protein level of TK1 in 62 CESC tissues and control tissues. The growth effect of TK1 and TK2 in CESC cell lines was assessed using Chronos dependency scores derived from CRISPR knockout screen in the Achilles project. We also analyzed the potential mechanism of TK genes by studying the relationship between TK gene expression and immune infiltration, gene alternations as well as the related signal pathways. Results: The various detection methods employed all confirmed that the TK1 expression is upregulated and TK2 is downregulated in CESC tissues (SMD: 2.44, 95% confidence interval (CI): 1.36 - 3.51, area under curve (AUC): 0.88, 95% CI: 0.85 - 0.90; SMD: -0.69, 95% CI: -1.25 to -0.14, AUC: 0.75, 95% CI: 0.71 - 0.78). Inhibition of TK1 expression by CRISPR knockout had negative influence on the biological functions of 11 CESC cell lines. The expression of TK2 was negatively correlated with the malignant progression of CESC. Expression of TK genes showed significant association with the immune infiltration of macrophages, CD4+ T cells, and neutrophils. Genes related with TK1 or TK2 were involved in pathways related to DNA replication, proteasome, and homologous recombination. Conclusions: Clinically, these findings suggest that the differential expression of TK1 and TK2 could serve as potential biomarkers, as well as therapeutic targets for personalized treatment strategies in CESC patients.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".