<i>ACTR10</i> Overexpression Facilitates the Progression and Tyrosine Kinase Inhibitor Resistance in Hepatocellular Carcinoma
Bibliographic record
Abstract
Background: In the present day, hepatocellular carcinoma (HCC) remains a formidable threat to human health. Actin-related protein 10 (ACTR10) is related to tyrosine kinase inhibitor (TKI) resistance. A comprehensive analysis of ACTR10 in HCC will further our understanding of the molecular mechanisms underlying this resistance phenomenon, shedding light on potential therapeutic strategies for combating TKI resistance in HCC. Methods: We conducted an integration of high-throughput datasets across various centers, analyzing ACTR10 expression using the Cancer Cell Line Encyclopedia (CCLE) and assessing its implications through clustered regularly interspaced short palindromic repeats (CRISPR) knockout screen. Pathogenic mechanisms were elucidated through enrichment analysis. Prognostic assessment utilized Kaplan-Meier survival and univariate Cox analyses. An integrated analysis of gene expression profiles related to TKI in HCC was conducted, and TKI resistance mechanisms were explored through enrichment analysis. Potential therapeutic drugs were identified using the Drug Gene Budger database and molecular docking techniques. Results: The standardized mean difference (SMD) of 0.34 (95% confidence interval (CI): 0.22 - 0.45, P < 0.05) and ACTR10-dependent growth in HCC cells confirm its upregulation in HCC. The area under the summary receiver operating characteristic (sROC) curve was 0.69, indicating moderate discriminative ability of ACTR10 in HCC patients. ACTR10 exerts its pro-cancer effect by influencing RNA splicing, mRNA processing and nucleocytoplasmic transport. A hazard ratio of 2.19 (95% CI: 1.56 - 3.08, P < 0.05) identifies ACTR10 as an independent prognostic risk factor. Additionally, the SMD of 0.88 (95% CI: 0.01 - 0.76, P < 0.05) validates ACTR10 as a TKI-resistance gene, mediating resistance via enhanced exocytosis, autophagy, and apoptosis in HCC patients. Trichostatin A emerges as a prospective targeted agent for HCC. Conclusion: The upregulation of ACTR10 accelerates HCC progression, promotes TKI resistance, and emerges as a prospective target for the treatment of HCC.
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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 | 0.001 | 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".