ScRNA-seq Revealed the Tumor Microenvironment Heterogeneity Related to the Occurrence and Metastasis in Upper Urinary Tract Urothelial Carcinoma

Overview

Journal Cancer Gene Ther

Specialties Genetics
Oncology
Pharmacology

Date 2024 Jun 14

PMID 38877164

Authors

Shiyong Xin

Yanwei Zhang

Zhenhua Zhang

Ziyao Li

Xianchao Sun

Xiang Liu

Liang Jin

Weiyi Li

Chaozhi Tang

Wangli Mei

Qiong Cao

Haojie Wang

Zhihao Wei

Zhen Zhou

Rongbing Li

Xiaofei Wen

Guosheng Yang

Weihua Chen

Junhua Zheng

Lin Ye

Affiliations

Soon will be listed here.

Abstract

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

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References

Siegel R, Miller K, Fuchs H, Jemal A . Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1):7-33. DOI: 10.3322/caac.21708. View

Hassler M, Bray F, Catto J, Grollman A, Hartmann A, Margulis V . Molecular Characterization of Upper Tract Urothelial Carcinoma in the Era of Next-generation Sequencing: A Systematic Review of the Current Literature. Eur Urol. 2020; 78(2):209-220. DOI: 10.1016/j.eururo.2020.05.039. View

Crivelli J, Xylinas E, Kluth L, Rieken M, Rink M, Shariat S . Effect of smoking on outcomes of urothelial carcinoma: a systematic review of the literature. Eur Urol. 2013; 65(4):742-54. DOI: 10.1016/j.eururo.2013.06.010. View

van Osch F, Jochems S, van Schooten F, Bryan R, Zeegers M . Significant Role of Lifetime Cigarette Smoking in Worsening Bladder Cancer and Upper Tract Urothelial Carcinoma Prognosis: A Meta-Analysis. J Urol. 2015; 195(4 Pt 1):872-9. DOI: 10.1016/j.juro.2015.10.139. View

Roupret M, Babjuk M, Burger M, Capoun O, Cohen D, Comperat E . European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update. Eur Urol. 2020; 79(1):62-79. DOI: 10.1016/j.eururo.2020.05.042. View

Laplane L, Duluc D, Bikfalvi A, Larmonier N, Pradeu T . Beyond the tumour microenvironment. Int J Cancer. 2019; 145(10):2611-2618. PMC: 6766895. DOI: 10.1002/ijc.32343. View

Huang C, Bruggeman L, Hydo L, Miller R . Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes. Exp Cell Res. 2012; 318(10):1075-85. PMC: 3345072. DOI: 10.1016/j.yexcr.2012.03.011. View

Ahn S, Park H . XIAP is essential for shear stress-enhanced Tyr-576 phosphorylation of FAK. Biochem Biophys Res Commun. 2010; 399(2):256-61. DOI: 10.1016/j.bbrc.2010.07.064. View

McGranahan N, Swanton C . Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future. Cell. 2017; 168(4):613-628. DOI: 10.1016/j.cell.2017.01.018. View

10.

McGranahan N, Swanton C . Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell. 2015; 27(1):15-26. DOI: 10.1016/j.ccell.2014.12.001. View

11.

Blanpain C . Tracing the cellular origin of cancer. Nat Cell Biol. 2013; 15(2):126-34. DOI: 10.1038/ncb2657. View

12.

Lourenco A, Ban Y, Crowley M, Lee S, Ramchandani D, Du W . Differential Contributions of Pre- and Post-EMT Tumor Cells in Breast Cancer Metastasis. Cancer Res. 2019; 80(2):163-169. PMC: 6980649. DOI: 10.1158/0008-5472.CAN-19-1427. View

13.

Davis R, Blake K, Ma D, Ishak Gabra M, Hernandez G, Phung A . Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing. Nat Cell Biol. 2020; 22(3):310-320. DOI: 10.1038/s41556-020-0477-0. View

14.

Muller M, Bird T, Nault J . The landscape of gene mutations in cirrhosis and hepatocellular carcinoma. J Hepatol. 2020; 72(5):990-1002. DOI: 10.1016/j.jhep.2020.01.019. View

15.

Rebouissou S, Nault J . Advances in molecular classification and precision oncology in hepatocellular carcinoma. J Hepatol. 2020; 72(2):215-229. DOI: 10.1016/j.jhep.2019.08.017. View

16.

Baslan T, Hicks J . Unravelling biology and shifting paradigms in cancer with single-cell sequencing. Nat Rev Cancer. 2017; 17(9):557-569. DOI: 10.1038/nrc.2017.58. View

17.

Patel A, Tirosh I, Trombetta J, Shalek A, Gillespie S, Wakimoto H . Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014; 344(6190):1396-401. PMC: 4123637. DOI: 10.1126/science.1254257. View

18.

Albini A, Sporn M . The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer. 2007; 7(2):139-47. DOI: 10.1038/nrc2067. View

19.

Quail D, Joyce J . Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013; 19(11):1423-37. PMC: 3954707. DOI: 10.1038/nm.3394. View

20.

Hosein A, Huang H, Wang Z, Parmar K, Du W, Huang J . Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution. JCI Insight. 2019; 5. PMC: 6777805. DOI: 10.1172/jci.insight.129212. View