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Integrated Analysis of Genomic and Transcriptomic Profiles Identified the Role of GTP Binding Protein-4 (GTPBP4) in Breast Cancer.

ABSTRACT: Purpose: To explore the significance of GTP-binding protein 4 (GTPBP4) in breast cancer. Methods: Firstly, GTPBP4 expression analysis was performed in TIMER and UALCAN databases. Subsequently, the TCGA cohort and multiple Gene Expression Omnibus Cohorts were used as validation for GTPBP4 expression. Besides, we also evaluated the diagnostic value of GTPBP4 in TCGA Cohort and multiple GEO Cohorts. The predictive effect of GTPBP4 in breast cancer was then assessed using survival analysis. Then we look at the role of GTPBP4 in the immune milieu and create a Nomogram to help patients with breast cancer understand their prognosis. Finally, in vitro tests were carried out to look at GTPBP4 expression and function in breast cancer cell lines. Results: GTPBP4 is an independent breast cancer prognostic factor that is upregulated in the disease (p < 0.05). Enrichment analysis showed that GTPBP4 was associated with multiple functions and pathways. In addition, GTPBP4 is associated with a variety of immune cell types (p < 0.05). PCR assay showed that GTPBP4 expression was up-regulated in breast cancer cell lines. The activity, migration, and proliferation of breast cancer cells were considerably reduced after GTPBP4 knockdown in the CCK-8, Transwell, and Scratch assays. Conclusions: Our research discovered a new breast cancer biomarker that can be used as a guide for breast cancer diagnosis and treatment.

SUBMITTER: Hu Y

PROVIDER: S-EPMC9243593 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Breast cancer is a profoundly heterogeneous disease with respect to biological and clinical behavior. Gene expression profiling has been used to dissect this complexity and stratify tumors into intrinsic gene expression subtypes associated with distinct biology, patient outcome and different genomic alterations. Additionally, breast tumors occurring in individuals with germline BRCA1 or BRCA2 mutations typically fall into distinct subtypes. We applied global DNA copy number and gene expression profiling in 359 breast tumors. All tumors were classified according to intrinsic gene expression subtypes and included cases from genetically predisposed women. The Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm was used to identify significant DNA copy number aberrations and genomic subgroups of breast cancer. We identified 31 genomic regions that were highly amplified in >1% of the 359 breast tumors. Several amplicons were found to co-occur, the 8p12 and 11q13.3 regions being the most frequent combination besides amplicons on the same chromosomal arm. Unsupervised hierarchical clustering with 133 significant GISTIC regions (66 and 67 with DNA copy number gain and loss, respectively) revealed six genomic subtypes, termed: 17q12, basal-complex, luminal-simple, luminal-complex, amplifier and mixed subtype. Four of them had striking similarity to intrinsic gene expression subtypes and showed association to conventional tumor biomarkers and clinical outcome. However, luminal A-classified tumors were distributed in two main genomic subtypes, luminal-simple and luminal-complex, the former group having better prognosis while the latter group included also luminal B and the majority of BRCA2-mutated tumors. The basal-complex subtype displayed extensive genomic homogeneity and harbored the majority of BRCA1-mutated tumors. The 17q12 subtype comprised mostly HER2-amplified and HER2-enriched subtype tumors and had the worst prognosis. The amplifier and mixed subtypes contained tumors from all gene expression subtypes, the former being enriched for 8p12-amplified cases while the mixed subtype included many tumors with predominantly DNA copy number losses and poor prognosis. Genomic profiling of 359 breast tumors using tiling BAC aCGH. A number of cases were hybridized as replicates or replicate as dye-swaps. Gene expression profiling of 359 breast tumors using 55K oligonucleotide microarrays.

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Integrated Analysis of Genomic and Transcriptomic Profiles Identified the Role of GTP Binding Protein-4 (GTPBP4) in Breast Cancer.

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