July 28, 2025

Aurka orchestrates colorectal cancer progression through dual regulation of tumor proliferation and immune microenvironment

YXYidong XuTongji University WWWei WangNingbo Medical Center Lihuili Hospital JYJiazi YuNingbo Medical Center Lihuili Hospital

Key Points

AURKA plays a dual role in regulating tumor proliferation and immune microenvironment in colorectal cancer.
Higher AURKA expression correlates with improved patient survival outcomes, particularly in immune therapy contexts.
Analysis included bulk and single-cell RNA sequencing, assessing T cell infiltration and prognostics in CRC.
These findings indicate AURKA as a potential target to enhance immunotherapy response in colorectal cancer patients.

Abstract

Abstract Background: The third most common malignancy globally, colorectal cancer (CRC), remains the leading cause of cancer-related mortality despite significant therapeutic advancements. Aurora Kinase A (AURKA) functions as a key molecular hub, influencing both its canonical role in cell proliferation and its modulation of the tumor microenvironment (TME). Although its dual roles in colorectal tumorigenesis remain partially characterized. Methods: We performed an integrated analysis of AURKA expression using bulk and single-cell RNA sequencing datasets in CRC. Immune cell infiltration was quantified via CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). Prognostic significance was evaluated using Kaplan–Meier survival analyses. Clinical validation employed hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) on CRC specimens. The association between AURKA and immunotherapy response was further investigated using publicly available immune checkpoint blockade (ICB) cohorts and a murine CRC model. Results: Pan-cancer analysis revealed AURKA regulation across gastrointestinal malignancies, with CRC exhibiting unique prognostic associations (P P=0.034). Pathway enrichment implicated AURKA in core cell cycle regulation (G2/M checkpoint, E2F targets) and immune-modulatory pathways (leukocyte migration, IL-2/STAT5 signaling). Validation experiment confirmed AURKA upregulation in CRC tissues and its positive correlation with CD4⁺ T-cell infiltration (transcriptomics: r = 0.62, P P P = 0.003). And murine model validation demonstrated elevated AURKA in immunotherapy responders, paralleling CD4⁺ memory T-cell expansion. Conclusion: AURKA serves as a dual modulator of tumor proliferation and immune engagement in CRC. Its expression reflects its role within the tumor microenvironment (TME) and T cell activity, with implications for targeting anti-PD-1 responses.

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