Prognostic Implications of Arginase and Cytokeratin 19 Expression in Hepatocellular Carcinoma After Curative Hepatectomy: Correlation With Recurrence-Free Survival
Bibliographic record
Abstract
BACKGROUND: The prognostic value of arginase expression in hepatocellular carcinoma (HCC) has been evaluated previously. However, no clear distinction exists yet on the role of arginase-1 as a predictor of recurrence in HCC. Cytokeratin 19 (CK19), a cholangiocytic marker, is occasionally expressed in HCC, but the combination of arginase-1 and CK19 expression has never been evaluated. The aim of the study was to investigate the usefulness of arginase-1 and CK19 expression alone and in combination for prognosticating HCC tumor recurrence after surgical resection. METHODS: Tissue sections from 112 HCCs were immunostained using an automated method and the mouse monoclonal arginase-1 and mouse monoclonal CK19 antibodies. The clinicopathologic variables, including alpha-fetoprotein levels, viral hepatitis, cirrhosis, tumor size, grade and number, vascular invasion, tumor-node-metastasis (TNM) stage, and tumor recurrence and survival, were obtained from each patient's medical records. The variables were assessed for correlation with the immunochemical results. Comparisons of recurrence-free and overall survival were performed using univariate and multivariate regression analyses. A P-value of ≤ 0.05 was considered statistically significant. RESULTS: High arginase-1 expression was detected in the HCCs of 93 patients (83%), whereas CK19 was positive in the HCCs of only 19 patients (17%). In the univariate analyses, CK19 positivity in HCC was associated with decreased recurrence-free survival compared with CK19-negative HCC (P = 0.0002). Arginase-1 expression was associated with decreased recurrence-free survival when patients were stratified over advanced TNM stage and presence of vascular invasion. The combination of arginase-1 and CK19 expression was a better predictor of decreased recurrence-free survival (P = 0.00008). Arginase-1/CK19 expressions when combined with multiple tumors, TNM stage and vascular invasion were also associated with decreased recurrence-free survival. In the multivariate analysis, tumor grade, CK19 and arginase-1/CK19 expressions were identified as independent prognostic indicators for decreased recurrence-free survival. CONCLUSION: Arginase-1 and CK19 combination immunoreactivity is a potential biomarker of adverse prognosis in HCC, correlating with the presence of multiple tumors, vascular invasion and advanced stage.
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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) | 0.000 | 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 | 0.001 |
| 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".