Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma
The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome,...
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/3045 |
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| author | Euiyoung Oh Jun-Hyeong Kim JungIn Um Da-Woon Jung Darren R. Williams Hyunju Lee |
| author_facet | Euiyoung Oh Jun-Hyeong Kim JungIn Um Da-Woon Jung Darren R. Williams Hyunju Lee |
| author_sort | Euiyoung Oh |
| collection | DOAJ |
| description | The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development. |
| first_indexed | 2024-03-10T10:17:26Z |
| format | Article |
| id | doaj.art-433bb3d874b7438093a9bafb7d12bf9f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:17:26Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-433bb3d874b7438093a9bafb7d12bf9f2023-11-22T00:42:39ZengMDPI AGCancers2072-66942021-06-011312304510.3390/cancers13123045Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell CarcinomaEuiyoung Oh0Jun-Hyeong Kim1JungIn Um2Da-Woon Jung3Darren R. Williams4Hyunju Lee5School of Electrical Engineering and Computer Science, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-Gu, Gwangju 61005, KoreaNew Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-Gu, Gwangju 61005, KoreaNew Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-Gu, Gwangju 61005, KoreaNew Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-Gu, Gwangju 61005, KoreaNew Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-Gu, Gwangju 61005, KoreaSchool of Electrical Engineering and Computer Science, Gwangju Institute of Science and Technology, 123 Cheomdangwagi-ro, Buk-Gu, Gwangju 61005, KoreaThe relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development.https://www.mdpi.com/2072-6694/13/12/3045transcriptomic analysisnormal tissueaging-related prognostic markersrenal cell carcinoma |
| spellingShingle | Euiyoung Oh Jun-Hyeong Kim JungIn Um Da-Woon Jung Darren R. Williams Hyunju Lee Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma Cancers transcriptomic analysis normal tissue aging-related prognostic markers renal cell carcinoma |
| title | Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma |
| title_full | Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma |
| title_fullStr | Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma |
| title_full_unstemmed | Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma |
| title_short | Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma |
| title_sort | genome wide transcriptomic analysis of non tumorigenic tissues reveals aging related prognostic markers and drug targets in renal cell carcinoma |
| topic | transcriptomic analysis normal tissue aging-related prognostic markers renal cell carcinoma |
| url | https://www.mdpi.com/2072-6694/13/12/3045 |
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