Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer
Abstract Although hormone therapy is effective for the treatment of prostate cancer (Pca), many patients develop a lethal type of Pca called castration-resistant prostate cancer (CRPC). Dysregulation of DNA damage response (DDR)-related genes leads to Pca progression. Here, we explored DDR-related s...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46651-6 |
| _version_ | 1797630218143268864 |
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| author | Masashi Oshima Ken-ichi Takayama Yuta Yamada Naoki Kimura Haruki Kume Tetsuya Fujimura Satoshi Inoue |
| author_facet | Masashi Oshima Ken-ichi Takayama Yuta Yamada Naoki Kimura Haruki Kume Tetsuya Fujimura Satoshi Inoue |
| author_sort | Masashi Oshima |
| collection | DOAJ |
| description | Abstract Although hormone therapy is effective for the treatment of prostate cancer (Pca), many patients develop a lethal type of Pca called castration-resistant prostate cancer (CRPC). Dysregulation of DNA damage response (DDR)-related genes leads to Pca progression. Here, we explored DDR-related signals upregulated in CRPC tissues. We analyzed the gene expression profiles in our RNA-sequence (RNA-seq) dataset containing benign prostate, primary Pca, and CRPC samples. We identified six DDR-related genes (Ribonuclease H2 Subunit A (RNASEH2A), replication factor C subunit 2 (RFC2), RFC4, DNA Ligase 1 (LIG1), DNA polymerase D1 (POLD1), and DNA polymerase E4 (POLE4)) that were upregulated in CRPC compared with Pca tissues. By analyzing public databases and validation studies, we focused on RFC2 as a new biomarker. Functional analysis demonstrated that silencing of RFC2 expression inhibited cell proliferation and induced the expression of DNA damage and apoptosis markers in CRPC model cells. Furthermore, immunohistochemical (IHC) analysis revealed that high expression of RFC2 protein correlated with poor prognosis in patients with Pca and increased expression in CRPC tissues compared with localized Pca. Thus, our study suggests that six DDR-related genes would be important for Pca progression. RFC2 could be a useful biomarker associated with poor outcomes of patients with Pca. |
| first_indexed | 2024-03-11T11:05:05Z |
| format | Article |
| id | doaj.art-27947c16400749ba8d5ee6964254ce1b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:05:05Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-27947c16400749ba8d5ee6964254ce1b2023-11-12T12:15:54ZengNature PortfolioScientific Reports2045-23222023-11-0113111410.1038/s41598-023-46651-6Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancerMasashi Oshima0Ken-ichi Takayama1Yuta Yamada2Naoki Kimura3Haruki Kume4Tetsuya Fujimura5Satoshi Inoue6Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and GerontologyDepartment of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and GerontologyDepartment of Urology, Graduate School of Medicine, The University of TokyoDepartment of Urology, Graduate School of Medicine, The University of TokyoDepartment of Urology, Graduate School of Medicine, The University of TokyoDepartment of Urology, Jichi Medical UniversityDepartment of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and GerontologyAbstract Although hormone therapy is effective for the treatment of prostate cancer (Pca), many patients develop a lethal type of Pca called castration-resistant prostate cancer (CRPC). Dysregulation of DNA damage response (DDR)-related genes leads to Pca progression. Here, we explored DDR-related signals upregulated in CRPC tissues. We analyzed the gene expression profiles in our RNA-sequence (RNA-seq) dataset containing benign prostate, primary Pca, and CRPC samples. We identified six DDR-related genes (Ribonuclease H2 Subunit A (RNASEH2A), replication factor C subunit 2 (RFC2), RFC4, DNA Ligase 1 (LIG1), DNA polymerase D1 (POLD1), and DNA polymerase E4 (POLE4)) that were upregulated in CRPC compared with Pca tissues. By analyzing public databases and validation studies, we focused on RFC2 as a new biomarker. Functional analysis demonstrated that silencing of RFC2 expression inhibited cell proliferation and induced the expression of DNA damage and apoptosis markers in CRPC model cells. Furthermore, immunohistochemical (IHC) analysis revealed that high expression of RFC2 protein correlated with poor prognosis in patients with Pca and increased expression in CRPC tissues compared with localized Pca. Thus, our study suggests that six DDR-related genes would be important for Pca progression. RFC2 could be a useful biomarker associated with poor outcomes of patients with Pca.https://doi.org/10.1038/s41598-023-46651-6 |
| spellingShingle | Masashi Oshima Ken-ichi Takayama Yuta Yamada Naoki Kimura Haruki Kume Tetsuya Fujimura Satoshi Inoue Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer Scientific Reports |
| title | Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer |
| title_full | Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer |
| title_fullStr | Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer |
| title_full_unstemmed | Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer |
| title_short | Identification of DNA damage response-related genes as biomarkers for castration-resistant prostate cancer |
| title_sort | identification of dna damage response related genes as biomarkers for castration resistant prostate cancer |
| url | https://doi.org/10.1038/s41598-023-46651-6 |
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