SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer
Abstract Background Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately. Methods We screened HRD-related ge...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03513-5 |
| _version_ | 1811293625438437376 |
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| author | Cong Luo Zhi Liu Yu Gan Xiaomei Gao Xiongbing Zu Ye Zhang Wenrui Ye Yi Cai |
| author_facet | Cong Luo Zhi Liu Yu Gan Xiaomei Gao Xiongbing Zu Ye Zhang Wenrui Ye Yi Cai |
| author_sort | Cong Luo |
| collection | DOAJ |
| description | Abstract Background Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately. Methods We screened HRD-related genes based on the HRD scores and constructed an HRD cluster system to explore different clinicopathological, genomic, and immunogenomic patterns among the clusters. A risk signature, HRDscore, was established and evaluated by multivariate Cox regression analysis. We noticed that SLC26A4, a model gene, demonstrated unique potential to predict prognosis and HRD in PCa. Multi-omics analysis was conducted to explore its role in PCa, and the results were validated by qRT-PCR and immunohistochemistry. Results Three HRD clusters were identified with significant differences in patient prognosis, clinicopathological characteristics, biological pathways, immune infiltration characteristics, and regulation of immunomodulators. Further analyses revealed that the constructed HRDscore system was an independent prognostic factor of PCa patients with good stability. Finally, we identified a single gene, SLC26A4, which significantly correlated with prognosis in three independent cohorts. Importantly, SLC26A4 was confirmed to distinguish PCa (AUC for mRNA 0.845; AUC for immunohistochemistry score 0.769) and HRD (AUC for mRNA 0.911; AUC for immunohistochemistry score 0.689) at both RNA and protein levels in our cohort. Conclusion This study introduces HRDscore to quantify the HRD pattern of individual PCa patients. Meanwhile, SLC26A4 is a novel biomarker and can reasonably predict the prognosis and HRD in PCa. |
| first_indexed | 2024-04-13T05:04:15Z |
| format | Article |
| id | doaj.art-28d0d384f2d4432e905530f4ad6ad6a3 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T05:04:15Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-28d0d384f2d4432e905530f4ad6ad6a32022-12-22T03:01:14ZengBMCJournal of Translational Medicine1479-58762022-07-0120111910.1186/s12967-022-03513-5SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancerCong Luo0Zhi Liu1Yu Gan2Xiaomei Gao3Xiongbing Zu4Ye Zhang5Wenrui Ye6Yi Cai7Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, Xiangya Hospital, Central South UniversityDepartment of Urology, Disorders of Prostate Cancer Multidisciplinary Team, Xiangya Hospital, Central South UniversityDepartment of Urology, Disorders of Prostate Cancer Multidisciplinary Team, Xiangya Hospital, Central South UniversityNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South UniversityDepartment of Urology, Disorders of Prostate Cancer Multidisciplinary Team, Xiangya Hospital, Central South UniversityNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South UniversityNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South UniversityDepartment of Urology, Disorders of Prostate Cancer Multidisciplinary Team, Xiangya Hospital, Central South UniversityAbstract Background Homologous recombination deficiency (HRD) is closely associated with patient prognosis and treatment options in prostate cancer (PCa). However, there is a lack of quantitative indicators related to HRD to predict the prognosis of PCa accurately. Methods We screened HRD-related genes based on the HRD scores and constructed an HRD cluster system to explore different clinicopathological, genomic, and immunogenomic patterns among the clusters. A risk signature, HRDscore, was established and evaluated by multivariate Cox regression analysis. We noticed that SLC26A4, a model gene, demonstrated unique potential to predict prognosis and HRD in PCa. Multi-omics analysis was conducted to explore its role in PCa, and the results were validated by qRT-PCR and immunohistochemistry. Results Three HRD clusters were identified with significant differences in patient prognosis, clinicopathological characteristics, biological pathways, immune infiltration characteristics, and regulation of immunomodulators. Further analyses revealed that the constructed HRDscore system was an independent prognostic factor of PCa patients with good stability. Finally, we identified a single gene, SLC26A4, which significantly correlated with prognosis in three independent cohorts. Importantly, SLC26A4 was confirmed to distinguish PCa (AUC for mRNA 0.845; AUC for immunohistochemistry score 0.769) and HRD (AUC for mRNA 0.911; AUC for immunohistochemistry score 0.689) at both RNA and protein levels in our cohort. Conclusion This study introduces HRDscore to quantify the HRD pattern of individual PCa patients. Meanwhile, SLC26A4 is a novel biomarker and can reasonably predict the prognosis and HRD in PCa.https://doi.org/10.1186/s12967-022-03513-5Homologous recombination deficiencyProstate cancerSLC26A4PrognosisPARP inhibitors |
| spellingShingle | Cong Luo Zhi Liu Yu Gan Xiaomei Gao Xiongbing Zu Ye Zhang Wenrui Ye Yi Cai SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer Journal of Translational Medicine Homologous recombination deficiency Prostate cancer SLC26A4 Prognosis PARP inhibitors |
| title | SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer |
| title_full | SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer |
| title_fullStr | SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer |
| title_full_unstemmed | SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer |
| title_short | SLC26A4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer |
| title_sort | slc26a4 correlates with homologous recombination deficiency and patient prognosis in prostate cancer |
| topic | Homologous recombination deficiency Prostate cancer SLC26A4 Prognosis PARP inhibitors |
| url | https://doi.org/10.1186/s12967-022-03513-5 |
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