ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Multi omics analysis and functional validation reveal the oncogenic role of TRIP13
1. Second Xiangya Hospital, Central South University, Changsha, China
2. The Second Xiangya Hospital of Central South University Department of Urology, Changsha, China
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Abstract
Background: Thyroid hormone receptor-interacting protein 13 (TRIP13), an enzyme from the AAA-ATPase family, facilitates the assembly or disassembly of protein complexes and participates in various biological processes. However, its impact on cancer immune infiltration and pan-cancer prognosis remains largely unexplored. Methods: Pan-cancer multi-omics data from publicly available resources were systematically analyzed to evaluate TRIP13 expression across various cancer types and its association with patient prognosis. In addition, functional enrichment analyses were conducted to investigate TRIP13 related biological processes and pathways. The analysis included GSEA enrichment, correlation with immune regulators expression, tumor immune cells infiltration, association with tumor mutational burden (TMB), and correlation with microsatellite instability (MSI). Additionally, single-cell data were used to explore the expression and potential role of TRIP13 at the single-cell level. We subsequently conducted a series of in vitro experiments. Results: Our comprehensive pan-cancer analysis reveals significantly elevated TRIP13 expression across multiple cancer types and links it to poor prognostic outcomes. TRIP13 primarily activates pathways such as ubiquitination, cell cycle regulation, and DNA repair to drive tumor progression. Additionally, TRIP13 expression exhibits complex associations with various immune regulators and immune cells. In prostate cancer, TRIP13 shows marked overexpression and associates with unfavorable prognosis. We identified a significant upregulation of TRIP13 in proliferative tumor stem like populations in prostate cancer. Consistently, prostate cancer cells that acquired resistance to CDK4/6 inhibitors displayed marked TRIP13 overexpression, and functional assays revealed that TRIP13 modulates cellular sensitivity to these agents. Mechanistically, we demonstrated that E2F1 transcriptionally activates TRIP13, which in turn drives the upregulation of the downstream ubiquitin ligase HECTD3. Conclusion: This study reveals aberrant TRIP13 expression across multiple cancers and its association with immune modulation and tumor aggressiveness. The elevation of TRIP13 in palbociclib resistant prostate cancer, together with the regulatory E2F1-TRIP13-HECTD3 axis, highlights its potential as a prognostic biomarker and therapeutic target.
Summary
Keywords
Immune infiltration, Palbociclib resistance, Pan-cancer, prognosis, prostate cancer, TRIP13
Received
23 August 2025
Accepted
18 February 2026
Copyright
© 2026 zhao, zhao, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: yuanqiao zhao; yongqi zhao
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