4.6 Article

Clinical Significance and Systematic Expression Analysis of the Thyroid Receptor Interacting Protein 13 (TRIP13) as Human Gliomas Biomarker

期刊

CANCERS
卷 13, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/cancers13102338

关键词

TRIP13; IDH; glioma; GBM

类别

资金

  1. Ministry of Science and Technology [MOST 106-2314-B-016-012-MY3, MOST 108-2314-B-016-026-MY3]
  2. Tri-Service General Hospital [TSGH-2-C107-106-2314-B-016-012-MY3, TSGH-C108-007-008-S05, TSGH-C01-109016, TSGH-C05-110034, TSGH-1-C110-108-2314-B-016-026-MY3, TSGH-D-109178]
  3. Medical Affairs Bureau, Ministry of National Defense [MAB-108-022, MAB-109-014, MND-MAB-110-115]

向作者/读者索取更多资源

High expression of TRIP13 in gliomas is associated with poor prognosis, potentially influencing tumor development by regulating co-expressed genes related to tumorigenesis and therapeutic resistance. Aberrant expression of TRIP13 may be regulated by mechanisms such as DNA methylation and miRNA targeting, leading to high aneuploidy levels and reduced CD8(+)/Treg ratio, which worsen patient outcomes.
Simple Summary High expression of TRIP13 is associated with IDH-wild type gliomas. Patients with elevated TRIP13 levels are indicative of the poor survival outcome. The study aimed to provide comprehensive information about the oncogenic potential of TRIP13 in clinical significance for gliomas. We found that TRIP13 co-expressed genes implicated in tumorigenesis and therapeutic resistance may regulated by TP53 and FOXM1. The aberrant expression of TRIP13 in gliomas was uncovered to be regulated by distinct underlying mechanisms, including the DNA methylation and dysfunction of miRNA targeting (such as miR-29 family). TRIP13-expressing tumors also showed high aneuploidy levels and reduced ratio of CD8(+)/Treg, which have unfavorable effects on patient outcome. These results demonstrate that TRIP13 is crucial for tumor development and reveal the emerging therapeutic potential of gliomas. The prognosis of malignant gliomas such as glioblastoma multiforme (GBM) has remained poor due to limited therapeutic strategies. Thus, it is pivotal to determine prognostic factors for gliomas. Thyroid Receptor Interacting Protein 13 (TRIP13) was found to be overexpressed in several solid tumors, but its role and clinical significance in gliomas is still unclear. Here, we conducted a comprehensive expression analysis of TRIP13 to determine the prognostic values. Gene expression profiles of the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and GSE16011 dataset showed increased TRIP13 expression in advanced stage and worse prognosis in IDH-wild type lower-grade glioma. We performed RT-PCR and Western blot to validate TRIP13 mRNA expression and protein levels in GBM cell lines. TRIP13 co-expressed genes via database screening were regulated by essential cancer-related upstream regulators (such as TP53 and FOXM1). Then, TCGA analysis revealed that more TRIP13 promoter hypomethylation was observed in GBM than in low-grade glioma. We also inferred that the upregulated TRIP13 levels in gliomas could be regulated by dysfunction of miR-29 in gliomas patient cohorts. Moreover, TRIP13-expressing tumors not only had higher aneuploidy but also tended to reduce the ratio of CD8(+)/Treg, which led to a worse survival outcome. Overall, these findings demonstrate that TRIP13 has with multiple functions in gliomas, and they may be crucial for therapeutic potential.

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