Abstract:

Systems biology provides a holistic and multilayered analytical framework for investigating the tumor microenvironment of endometrial cancer (EC) by integrating genomics, transcriptomics, proteomics, metabolomics, and microbiomics. Current evidence indicates that genomics reveals the molecular classification characteristics of EC and their association with immune-related microenvironmental heterogeneity. Transcriptomics, particularly single-cell RNA sequencing and spatial transcriptomic technologies, deepens the understanding of tumor cell heterogeneity, spatial distribution, and cellular communication networks. Proteomics and metabolomics supplement the comprehension of EC invasive phenotypes, risk stratification, and prognostic differences from the perspectives of functional protein alterations and metabolic reprogramming, respectively. Microbiomics suggests that imbalances in gut and reproductive tract microbiota may participate in tumor microenvironment remodeling through inflammatory responses, immune regulation, and barrier dysfunction. Overall, multi-omics studies continuously enhance our knowledge of molecular heterogeneity and microenvironmental interaction mechanisms in EC, providing new bases for early identification, molecular classification, risk assessment, and individualized treatment. However, current challenges remain, including difficulties in multi-omics data integration, considerable heterogeneity in results, insufficient standardization, and limited evidence for clinical translation. Future efforts should strengthen the combined application of high-resolution single-cell and spatial multi-omics technologies and advance the standardized integration and prospective validation of multi-omics data to promote precise stratification and therapeutic optimization for EC.

Key words: Endometrial neoplasms, Systems biology, Tumor microenvironment, Genomics, Proteomics, Metabolomics