ArticleJournal of translational medicine2025
Multi-omics integration and machine learning uncover molecular basal-like subtype of pancreatic cancer and implicate A2ML1 in promoting tumor epithelial-mesenchymal transition.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Interleukin-1α (IL-1α) in pancreatic ductal adenocarcinoma: implications for immunotherapy and molecular biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Deep Generative and Graph-Based Representation Learning for Multiomics Survival Stratification in Ovarian Cancer: Secondary Analysis.JMIR bioinformatics and biotechnology · 2026Article
- COLEC12 promotes pancreatic cancer progression via the activation of the TGF-β signaling pathway.Molecular and cellular biochemistry · 2026Article
- Integrative multi-omics analysis identifies ATAD1 as a potential regulator of metastasis in pancreatic cancer.Scientific reports · 2026Article
- Machine learning-based clinical prediction model and multi-omics integration for assessing pancreatic cancer risk in new-onset diabetes.Journal of translational medicine · 2026Article
- Machine learning identifies disulfidptosis-related gene signature for pancreatic cancer prognosis and immune infiltration.Discover oncology · 2026Article
- Review
- Integrative multi-omics profiling reveals coordinated immunometabolic reprogramming and host-microbiome interactions in acute pancreatitis.Frontiers in immunology · 2026Article
- TRIM21 as a potential prognostic biomarker and therapeutic target affects the growth of pancreatic cancer.Discover oncology · 2025Article
- An exploratory study on the potential of angiogenic genes in early HNSCC detection.Discover oncology · 2025Article
- Multi-omics analyses inform mechanisms of immunotherapy response in pancreatic cancer.Frontiers in immunology · 2025Article
- The place of advanced machine learning techniques in building pancreatic adenocarcinoma survival and recurrence prognosis models.Frontiers in oncology · 2025Review
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Authors and funding
5 authors.
Funding
Abstract
backgroundPancreatic cancer (PC) represents a highly heterogeneous malignancy with poor prognosis, where precise molecular subtyping facilitates comprehensive understanding of disease progression.
methodsTranscriptomic, methylation, and mutational data from 168 PC samples were integrated. The molecular subtypes were established and validated across 13 independent cohorts utilizing ten distinct classification methods. Prognostic genes were identified to construct predictive models through various machine learning approaches. Following the identification of A2ML1 as a key gene, its expression profile was detected using RT-qPCR, western blotting, and immunohistochemistry. We subsequently conducted functional experiments to elucidate the mechanism of A2ML1 in promoting PC progression.
resultsThrough multi-omics integration, we classified PC into two molecular subtypes with distinct prognostic outcomes. Pathway enrichment analysis revealed subtype-specific characteristics, subsequently validated in external cohorts. Using 23 prognostic genes, we developed and validated a prognostic signature through 101 machine learning algorithms and their combinations, with ridge regression demonstrating optimal performance. This signature demonstrated superior accuracy compared to multiple published signatures. The risk scores showed significant correlations with drug sensitivity, clinical characteristics, and patient outcomes. We further validated that A2ML1 expression was significantly elevated in PC tissues compared to normal counterparts. A2ML1 promoted PC progression through downregulation of LZTR1 expression and subsequent activation of the KRAS/MAPK pathway, ultimately driving epithelial-mesenchymal transition (EMT).
conclusionIn this study, we uncovered molecular basal-like subtype of PC and developed a prognostic signature using ridge regression. A2ML1 was identified as a crucial regulator of EMT in PC progression.
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