Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance

Hany A Abdel-Hafiz; Saravana Kumar Kailasam Mani; Wesley Huang; Kenneth H Gouin 3rd; Yuzhou Chang; Tong Xiao; Qin Ma; Zihai Li; Simon R V Knott; Dan Theodorescu

doi:10.1016/j.isci.2023.107703

Single-cell profiling of murine bladder cancer identifies sex-specific transcriptional signatures with prognostic relevance

iScience. 2023 Aug 23;26(9):107703. doi: 10.1016/j.isci.2023.107703. eCollection 2023 Sep 15.

Authors

Hany A Abdel-Hafiz^{1

2

3}, Saravana Kumar Kailasam Mani¹, Wesley Huang^{1

4}, Kenneth H Gouin 3rd^{1

4}, Yuzhou Chang⁵, Tong Xiao⁵, Qin Ma⁵, Zihai Li⁵, Simon R V Knott^{3

4}, Dan Theodorescu^{1

3

6}

Affiliations

¹ Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
² Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
³ Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA.
⁴ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁵ Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center - The James, Columbus, OH 43210, USA.
⁶ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Abstract

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.

Keywords: Cancer; Cancer systems biology; Immunology.

Abstract

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