Single-Cell Multi-omics Decodes the Aggrephagy Landscape, Unveiling TUBA4A as a Novel Oncogene and Immunotherapeutic Target in ccRCC
Abstract
Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy with a complex and immunosuppressive tumor microenvironment (TME). While aggrephagy, a selective autophagy process, has been linked to cancer, its role in ccRCC remains unclear. Through integrated multi-omics analysis of single-cell and bulk sequencing data, we constructed the first aggrephagy activity atlas in ccRCC TME, revealing subtype-specific programs linked to immune suppression and metabolic reprogramming. High aggrephagy activity correlated with poor prognosis and immunotherapy resistance, particularly in macrophages and T cells. Among key prognostic genes, we identified TUBA4A as a novel player in ccRCC. Functional validation showed that TUBA4A enhances autophagy and promotes tumor proliferation, migration, and invasion. This study establishes aggrephagy and TUBA4A as key regulators of ccRCC progression and potential therapeutic targets.
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The authors declare no competing interests to disclose.
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