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Multi-omics approaches reveal erythroid progenitor cell in cancer: from passive bystander to active player

Abstract

Cancer remains a leading cause of human mortality worldwide, imposing a substantial public health burden. A deep understanding of the tumor microenvironment (TME) is essential for improving cancer care. Erythroid progenitor cells (EPCs) were traditionally viewed solely as intermediates in erythropoiesis; however, growing evidence indicates their active involvement in cancer progression and immune evasion. Research on EPCs increasingly utilizes omics sequencing technologies. Multi-omics strategies in particular enable in-depth investigation of the functional mechanisms of EPCs and their interactions with tumor and immune cells. This review examines various omics methodologies applied to EPCs from an oncology perspective, including transcriptomics, proteomics, epigenomics, and metabolomics, while critically assessing the advantages and limitations of each approach. Furthermore, it synthesizes how the integration of multiple omics technologies provides a more comprehensive view of EPC biology, particularly through complementary data modalities. This review also discusses artificial intelligence (AI)-powered multi-omics integration strategies and explore the translational potential of EPC-focused research in advancing cancer therapeutics from bench to bedside.

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Fig. 1: Overview of multi-omics for decoding EPCs in cancer.
Fig. 2: EPCs in physiological and cancerous contexts.
Fig. 3: Decoding the origins and heterogeneity of EPCs in cancer through multi-omics strategies.
Fig. 4: AI-powered multi-omics integrative analysis of EPCs.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (82273202); the Fundamental Research Funds for the Central Universities (2042022dx0003).

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Zi-Zhan Li: Writing – review & editing, Writing – original draft, Visualization, Validation, Software, Resources, Investigation. Cheng-Ke Zhou: Writing – original draft, Visualization, Software, Conceptualization, Writing – review & editing. Zhi-Jun Sun: Writing – review & editing, Conceptualization, Supervision, Investigation, Funding acquisition.

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Correspondence to Zhi-Jun Sun.

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Li, ZZ., Zhou, CK. & Sun, ZJ. Multi-omics approaches reveal erythroid progenitor cell in cancer: from passive bystander to active player. Oncogene (2026). https://doi.org/10.1038/s41388-026-03758-0

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