ArticleClinical and translational medicine2022
Multi-omics analysis of intra-tumoural and inter-tumoural heterogeneity in pancreatic ductal adenocarcinoma.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Purity Independent Subtyping of Tumors (PurIST) Pancreatic Cancer Classifier: Analytic Validation of a 16-RNA Expression Signature Distinguishing Basal and Classical Subtypes.The Journal of molecular diagnostics : JMD · 2024Trial
- Molecular mechanisms and therapeutic strategies: DNA methylation in pancreatic cancer.Cancer biology & therapy · 2026Review
- Tumor slice cultures enable rapid ex vivo profiling of patient-specific drug sensitivity in pancreatic ductal adenocarcinoma.NPJ precision oncology · 2026Article
- Stimulus-Responsive Polymeric Carriers for Gene Delivery: Balancing Endosomal Escape with Nucleic Acid Release.Pharmaceutical research · 2026Review
- The evolving role of OMICS in gastrointestinal tumor biology and clinical practice.Molecular cancer · 2026Review
- Deciphering the Heterogeneity of Pancreatic Cancer: DNA Methylation-Based Cell Type Deconvolution Unveils Distinct Subgroups and Immune Landscapes.Epigenomes · 2025Article
- In-depth patient-specific analysis of tumor heterogeneity in melanoma brain metastasis: Insights from spatial transcriptomics and multi-region bulk sequencing.Translational oncology · 2025Article
- Epigenetic evolution and clinicopathological implications of distinct DNA methylation profiles in pancreatic ductal adenocarcinoma.Scientific reports · 2025Article
- Clinical characteristics, prognosis, and nomogram for upper esophageal cancer: a SEER database analysis.Scientific reports · 2025Article
- Anoikis-related PLCB4 is linked to immunotherapy response in osteosarcoma.Discover oncology · 2025Article
- Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method.Pharmaceuticals (Basel, Switzerland) · 2025Review
- From Images to Genes: Radiogenomics Based on Artificial Intelligence to Achieve Non-Invasive Precision Medicine in Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Meta-analysis of multi-center transcriptomic profiles and machine learning reveal phospholipase Cβ4 as a Wnt/Ca²Frontiers in immunology · 2025Article
- Machine learning-based identification of biomarkers and drugs in immunologically cold and hot pancreatic adenocarcinomas.Journal of translational medicine · 2024Article
- Article
- Resolving tumor evolution: a phylogenetic approach.Journal of the National Cancer Center · 2024Review
- Identification and validation of neutrophils-related subtypes and prognosis model in triple negative breast cancer.Journal of cancer research and clinical oncology · 2024Article
- S100P as a potential biomarker for immunosuppressive microenvironment in pancreatic cancer: a bioinformatics analysis and in vitro study.BMC cancer · 2023Article
- Single-Cell Lipidomics Using Analytical Flow LC-MS Characterizes the Response to Chemotherapy in Cultured Pancreatic Cancer Cells.Analytical chemistry · 2023Article
- Intertumoral heterogeneity impacts oncolytic vesicular stomatitis virus efficacy in mouse pancreatic cancer cells.Journal of virology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is associated with the tumour heterogeneity. To explore intra- and inter-tumoural heterogeneity in PDAC, we analysed the multi-omics profiles of 61 PDAC lesion samples, along with the matched pancreatic normal tissue samples, from 19 PDAC patients. Haematoxylin and Eosin (H&E) staining revealed that diversely differentiated lesions coexisted both within and across individual tumours. Whole exome sequencing (WES) of samples from multi-region revealed diverse types of mutations in diverse genes between cancer cells within a tumour and between tumours from different individuals. The copy number variation (CNV) analysis also showed that PDAC exhibited intra- and inter-tumoural heterogeneity in CNV and that high average CNV burden was associated poor prognosis of the patients. Phylogenetic tree analysis and clonality/timing analysis of mutations displayed diverse evolutionary pathways and spatiotemporal characteristics of genomic alterations between different lesions from the same or different tumours. Hierarchical clustering analysis illustrated higher inter-tumoural heterogeneity than intra-tumoural heterogeneity of PDAC at the transcriptional levels as lesions from the same patients are grouped into a single cluster. Immune marker genes are differentially expressed in different regions and tumour samples as shown by tumour microenvironment (TME) analysis. TME appeared to be more heterogeneous than tumour cells in the same patient. Lesion-specific differentially methylated regions (DMRs) were identified by methylated DNA immunoprecipitation sequencing (MeDIP-seq). Furthermore, the integration analysis of multi-omics data showed that the mRNA levels of some genes, such as PLCB4, were significantly correlated with the gene copy numbers. The mRNA expressions of potential PDAC biomarkers ZNF521 and KDM6A were correlated with copy number alteration and methylation, respectively. Taken together, our results provide a comprehensive view of molecular heterogeneity and evolutionary trajectories of PDAC and may guide personalised treatment strategies in PDAC therapy.
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