Oncogenic function and transcriptional dynamics of MYCN in liver tumorigenesis - PubMed
5 days ago
- #tumor microenvironment
- #MYCN
- #liver cancer
- Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, often diagnosed at advanced stages with high recurrence rates.
- MYCN, a proto-oncogenic transcription factor, is identified as a potential biomarker of cancer stemness, though its role in hepatocarcinogenesis was unclear.
- The study demonstrates that MYCN overexpression synergizes with AKT activation to promote liver tumorigenesis in mice.
- Transcriptomic profiling showed MYCN-driven tumors resemble human HCC subtypes with stress-adaptive transcriptional programs.
- Time-resolved spatial transcriptomics revealed a MYCN-enriched niche with EMT and Wnt/β-catenin signaling, expanding during tumor progression.
- A machine learning-based MYCN niche score was developed and validated across human HCC cohorts, predicting recurrence risk and EMT-prone microenvironments.
- The MYCN niche score showed stronger predictive performance in nontumor tissues, suggesting its utility in detecting precancerous niches.
- The findings establish MYCN as a functional driver and spatial marker of tumor-promoting microenvironments in liver tumorigenesis.