Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma
Abstract Based on the epidemiological characteristics of susceptibility and age selectivity for women in Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we inferred that estrogen was to be blamed. Rad54 like 2 (Rad54l2) which might be one of key effector proteins of DNA damage mediated by e...
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33363-0 |
| _version_ | 1827966363620081664 |
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| author | Yanwen Lu Yiqi Zhu Wenliang Ma Ning Liu Xiang Dong Qiancheng Shi Fei Yu Hongqian Guo Dongmei Li Weidong Gan |
| author_facet | Yanwen Lu Yiqi Zhu Wenliang Ma Ning Liu Xiang Dong Qiancheng Shi Fei Yu Hongqian Guo Dongmei Li Weidong Gan |
| author_sort | Yanwen Lu |
| collection | DOAJ |
| description | Abstract Based on the epidemiological characteristics of susceptibility and age selectivity for women in Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we inferred that estrogen was to be blamed. Rad54 like 2 (Rad54l2) which might be one of key effector proteins of DNA damage mediated by estrogen was downregulated in numerous cancers, however, its role in epidemiological characteristics of Xp11.2 tRCC was needed to further study. We reviewed 1005 Xp11.2 tRCC cases and collected estrogen data and then compared the onset time of Xp11.2 tRCC cases in female with estrogen changing trend. An RNA-sequencing was performed in estrogen treated HK-2 cells and subsequently bioinformatic analysis was applied based on the Cancer Genome Atlas (TCGA) and GEO database. The male-to-female ratio of Xp11.2 tRCC was 1:1.4 and the median age of onset was 29.7 years old. The onset trend of female was similar to estrogen physiological rhythm (r = 0.67, p < 0.01). In Xp11.2 tRCC and HK-2 cells after estrogen treatment, Rad54l2 was downregulated, and GSEA showed that pathways significantly enriched in DNA damage repair and cancer related clusters after estrogen treated, as well as GO and KEGG analysis. Downregulation of Rad54l2 was in numerous cancers, including renal cell carcinoma (RCC), in which Rad54l2 expression was significantly decreased in male, age over 60 years old, T2&T3&T4 stages, pathologic SII&SIII&SIV stages as well as histologic G3&G4 grades, and cox regression analysis proved that Rad54l2 expression was a risk factor for overall survival, disease-specific survival and progression-free interval in univariate analysis. There existed female predominance in Xp11.2 tRCC and Rad54l2 might play vital role in estrogen mediating female predominance in Xp11.2 tRCC. |
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| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T17:47:44Z |
| publishDate | 2023-04-01 |
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| spelling | doaj.art-f3efcb5db0554c87a3524e1929e3320b2023-04-16T11:14:27ZengNature PortfolioScientific Reports2045-23222023-04-0113111410.1038/s41598-023-33363-0Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinomaYanwen Lu0Yiqi Zhu1Wenliang Ma2Ning Liu3Xiang Dong4Qiancheng Shi5Fei Yu6Hongqian Guo7Dongmei Li8Weidong Gan9Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Laboratory Medicine, Nanjing Children’s Hospital, The Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolImmunology and Reproduction Biology Laboratory and State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing UniversityDepartment of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolAbstract Based on the epidemiological characteristics of susceptibility and age selectivity for women in Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we inferred that estrogen was to be blamed. Rad54 like 2 (Rad54l2) which might be one of key effector proteins of DNA damage mediated by estrogen was downregulated in numerous cancers, however, its role in epidemiological characteristics of Xp11.2 tRCC was needed to further study. We reviewed 1005 Xp11.2 tRCC cases and collected estrogen data and then compared the onset time of Xp11.2 tRCC cases in female with estrogen changing trend. An RNA-sequencing was performed in estrogen treated HK-2 cells and subsequently bioinformatic analysis was applied based on the Cancer Genome Atlas (TCGA) and GEO database. The male-to-female ratio of Xp11.2 tRCC was 1:1.4 and the median age of onset was 29.7 years old. The onset trend of female was similar to estrogen physiological rhythm (r = 0.67, p < 0.01). In Xp11.2 tRCC and HK-2 cells after estrogen treatment, Rad54l2 was downregulated, and GSEA showed that pathways significantly enriched in DNA damage repair and cancer related clusters after estrogen treated, as well as GO and KEGG analysis. Downregulation of Rad54l2 was in numerous cancers, including renal cell carcinoma (RCC), in which Rad54l2 expression was significantly decreased in male, age over 60 years old, T2&T3&T4 stages, pathologic SII&SIII&SIV stages as well as histologic G3&G4 grades, and cox regression analysis proved that Rad54l2 expression was a risk factor for overall survival, disease-specific survival and progression-free interval in univariate analysis. There existed female predominance in Xp11.2 tRCC and Rad54l2 might play vital role in estrogen mediating female predominance in Xp11.2 tRCC.https://doi.org/10.1038/s41598-023-33363-0 |
| spellingShingle | Yanwen Lu Yiqi Zhu Wenliang Ma Ning Liu Xiang Dong Qiancheng Shi Fei Yu Hongqian Guo Dongmei Li Weidong Gan Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma Scientific Reports |
| title | Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma |
| title_full | Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma |
| title_fullStr | Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma |
| title_full_unstemmed | Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma |
| title_short | Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma |
| title_sort | estrogen associates with female predominance in xp11 2 translocation renal cell carcinoma |
| url | https://doi.org/10.1038/s41598-023-33363-0 |
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