Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma
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...
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MDPI AG
2022-10-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/11/1742 |
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| author | Chun-Chi Chen Pei-Yi Chu Hung-Yu Lin |
| author_facet | Chun-Chi Chen Pei-Yi Chu Hung-Yu Lin |
| author_sort | Chun-Chi Chen |
| collection | DOAJ |
| description | 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/β-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/β-catenin pathway and lipid metabolic processes. |
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| last_indexed | 2024-03-09T18:56:04Z |
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| spelling | doaj.art-b7e08ffa493d4559adafa41afe8e97092023-11-24T05:30:13ZengMDPI AGLife2075-17292022-10-011211174210.3390/life12111742Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate AdenocarcinomaChun-Chi Chen0Pei-Yi Chu1Hung-Yu Lin2Section of Urology, Departments of Surgery, Changhua Christian Hospital, Changhua 500, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, TaiwanResearch Assistant Center, Show Chwan Memorial Hospital, Changhua 500, TaiwanProstate 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/β-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/β-catenin pathway and lipid metabolic processes.https://www.mdpi.com/2075-1729/12/11/1742prostate adenocarcinomaATPase Family AAA Domain Containing 1biomarkerdeep deletionETS transcription factor ERGtranscription repression |
| spellingShingle | Chun-Chi Chen Pei-Yi Chu Hung-Yu Lin Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma Life prostate adenocarcinoma ATPase Family AAA Domain Containing 1 biomarker deep deletion ETS transcription factor ERG transcription repression |
| title | Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma |
| title_full | Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma |
| title_fullStr | Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma |
| title_full_unstemmed | Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma |
| title_short | Multi-Omics Analysis Reveals Clinical Value and Possible Mechanisms of ATAD1 Down-Regulation in Human Prostate Adenocarcinoma |
| title_sort | multi omics analysis reveals clinical value and possible mechanisms of atad1 down regulation in human prostate adenocarcinoma |
| topic | prostate adenocarcinoma ATPase Family AAA Domain Containing 1 biomarker deep deletion ETS transcription factor ERG transcription repression |
| url | https://www.mdpi.com/2075-1729/12/11/1742 |
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