Abstract B76: Characterizing vascular invasion in hepatoblastoma
Bibliographic record
Abstract
Abstract Hepatoblastoma (HB) is the most common pediatric liver malignancy, and patients with high-risk, metastatic disease have a five-year overall survival (OS) of only about 40%. Of note, HB patients with vascular invasion (VI) have a much worse OS. Our hypothesis is that HB tumors with VI possess unique clones that invade the vasculature, resulting in dissemination of disease. We injected the aggressive HepT1 cell line with confirmed CTNNB1 and NFE2L2 mutations in the livers of immunocompromised NSG mice to generate intrahepatic tumors. After 4 weeks, we had 100% take of tumors in animals. Serum human α-fetoprotein (AFP) increased with the growth of tumors. At time of death, we saw clear presence of intrahepatic VI, vena caval tumor thrombus, extrahepatic disease including within periportal lymph nodes, and lung metastasis in animals with tumors. We grew adherent and nonadherent cell lines from tumor samples, including one cell line from intrahepatic VI and one from vena caval tumor thrombus. Cells derived from VI areas had obvious differences in phenotype from cells from the primary tumor (PT). To further pursue these provocative changes between PT and VI areas, we generated two unique patient-derived xenograft (PDX) models of HB with intrahepatic implantation of PT and VI tumor samples from a nonmetastatic pretreatment extent of disease (PRETEXT) stage 4 patient. Mice harboring the VI PDX showed serum elevation of human AFP and obvious tumor with MRI. PT and VI PDX tissues expressed established HB markers nuclear Beta-catenin, Glypican-3, and AFP, resembling the primary patient sample. We also developed a novel cell line with growth of cells from a VI tumor in vitro. With both the HepT1 and PDX models, gene set enrichment transcriptomic analyses of RNA sequencing data showed clear changes in expression in aggressive tissues that invaded vessels, including significant (p<0.05) changes in pathways associated with liver damage, inflammation, and metabolism. Further exploration of these pathways and agents that target these pathways could improve outcomes for HB patients with invasive disease. Citation Format: Sarah E. Woodfield, Roma H. Patel, Aryana M. Ibarra, Barry Zorman, Andrew Badachhape, Ketan B. Ghaghada, Dolores Lopez-Terrada, Pavel Sumazin, Sanjeev A. Vasudevan. Characterizing vascular invasion in hepatoblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B76.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.002 | 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".