Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance
Summary: Bladder cancer (BLCA) is more common in men but more aggressive in women. Sex-based differences in cancer biology are commonly studied using a murine model with BLCA generated by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). While tumors in the BBN model have been profiled, these profiles p...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223017807 |
| _version_ | 1827824096992296960 |
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| author | Hany A. Abdel-Hafiz Saravana Kumar Kailasam Mani Wesley Huang Kenneth H. Gouin, III Yuzhou Chang Tong Xiao Qin Ma Zihai Li Simon R.V. Knott Dan Theodorescu |
| author_facet | Hany A. Abdel-Hafiz Saravana Kumar Kailasam Mani Wesley Huang Kenneth H. Gouin, III Yuzhou Chang Tong Xiao Qin Ma Zihai Li Simon R.V. Knott Dan Theodorescu |
| author_sort | Hany A. Abdel-Hafiz |
| collection | DOAJ |
| description | Summary: Bladder cancer (BLCA) is more common in men but more aggressive in women. Sex-based differences in cancer biology are commonly studied using a murine model with BLCA generated by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). While tumors in the BBN model have been profiled, these profiles provide limited information on the tumor microenvironment. Here, we applied single-cell RNA sequencing to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. We found proportional and gene expression differences in epithelial and non-epithelial subpopulations between male and female tumors. Expression of several genes predicted sex-specific survival in several human BLCA datasets. We identified novel and clinically relevant sex-specific transcriptional signatures including immune cells in the tumor microenvironment and it validated the relevance of the BBN model for studying sex differences in human BLCA. This work highlights the importance of considering sex as a biological variable in the development of new and accurate cancer markers. |
| first_indexed | 2024-03-12T02:21:08Z |
| format | Article |
| id | doaj.art-60e945995e5947319d89922d0132a23c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T02:21:08Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-60e945995e5947319d89922d0132a23c2023-09-06T04:52:46ZengElsevieriScience2589-00422023-09-01269107703Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevanceHany A. Abdel-Hafiz0Saravana Kumar Kailasam Mani1Wesley Huang2Kenneth H. Gouin, III3Yuzhou Chang4Tong Xiao5Qin Ma6Zihai Li7Simon R.V. Knott8Dan Theodorescu9Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USADepartment of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USADepartment of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USAPelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center – The James, Columbus, OH 43210, USAPelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center – The James, Columbus, OH 43210, USAPelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center – The James, Columbus, OH 43210, USAPelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center – The James, Columbus, OH 43210, USACedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Corresponding authorDepartment of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Corresponding authorSummary: Bladder cancer (BLCA) is more common in men but more aggressive in women. Sex-based differences in cancer biology are commonly studied using a murine model with BLCA generated by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). While tumors in the BBN model have been profiled, these profiles provide limited information on the tumor microenvironment. Here, we applied single-cell RNA sequencing to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. We found proportional and gene expression differences in epithelial and non-epithelial subpopulations between male and female tumors. Expression of several genes predicted sex-specific survival in several human BLCA datasets. We identified novel and clinically relevant sex-specific transcriptional signatures including immune cells in the tumor microenvironment and it validated the relevance of the BBN model for studying sex differences in human BLCA. This work highlights the importance of considering sex as a biological variable in the development of new and accurate cancer markers.http://www.sciencedirect.com/science/article/pii/S2589004223017807CancerCancer systems biologyImmunology |
| spellingShingle | Hany A. Abdel-Hafiz Saravana Kumar Kailasam Mani Wesley Huang Kenneth H. Gouin, III Yuzhou Chang Tong Xiao Qin Ma Zihai Li Simon R.V. Knott Dan Theodorescu Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance iScience Cancer Cancer systems biology Immunology |
| title | Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance |
| title_full | Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance |
| title_fullStr | Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance |
| title_full_unstemmed | Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance |
| title_short | Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance |
| title_sort | single cell profiling of murine bladder cancer identifies sex specific transcriptional signatures with prognostic relevance |
| topic | Cancer Cancer systems biology Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223017807 |
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