國家衛生研究院 NHRI:Item 3990099045/14678
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    題名: Multi-omics analysis reveals clinical value and possible mechanisms of ATAD1 down-regulation in human prostate adenocarcinoma
    作者: Chen, CC;Chu, PY;Lin, HY
    貢獻者: National Institute of Cancer Research
    摘要: Prostate adenocarcinoma (PRAD) is the most common histological subtype of prostate cancer. Post-treatment biochemical recurrence is a challenging issue. ATAD1 (ATPase Family AAA Domain Containing 1) plays a vital role in mitochondrial proteostasis and apoptosis activity, while its clinical value in PRAD and its impact on the tumor microenvironment (TME) remain unanswered. In this study, we aimed to investigate the clinical value and possible mechanisms of ATAD1 in PRAD via multi-omics analysis. Using cBioPortal, we confirmed that ATAD1 alteration was associated with gene expression and unfavorable DFS. Deep deletion predominantly occurred in PRAD. By integrating DriverDBv3 and GEPIA2, we noted ATAD1 downregulation in PRAD tissues compared to normal tissues, associated with unfavorable DFS in PRAD patients. DNA repair genes ATM, PARP1and BRCA2 had positive associations with ATAD1 expression. We found that the generalization value of ATAD1 could be applied to other cancers such as KIRC and UCEC. In addition, LinkedOmics identified that the functional involvement of ATAD1 participates in mitochondrial structure and cell cycle progression. Using TIMER analysis, we demonstrated that ATAD1 downregulation correlated with an immunosuppressive TME. Furthermore, we accessed a GSE55062 dataset on UALCAN and discovered the involvement of ERG-mediated transcriptional repression on ATAD1 downregulation. Cross-association screening of shATAD1 efficacy vs. altered mRNAs identified 190 perturbed mRNAs. Then, functional enrichment analysis using the Metascape omics tool recognized that shATAD1-perturbed mRNAs are primarily in charge of the activation of Wnt/beta-catenin pathway and lipid metabolic processes. In conclusion, multi-omics results reveal that ATAD1 downregulation is a clinical biomarker for pathological diagnosis and prognosis for patients with PRAD. Reduced ATAD1 may be involved in the enhanced activity of mitochondria and cell cycle, as well as possibly shaping an immunosuppressive TME. ERG serves as an upstream transcriptional repressor of ATAD1. Downstream mechanisms of ATAD1 are involved in Wnt/beta-catenin pathway and lipid metabolic processes.
    日期: 2022-10-30
    關聯: Life. 2022 Oct 30;12(11):Article number 1742.
    Link to: http://dx.doi.org/10.3390/life12111742
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2075-1729&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000881211300001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85141715591
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