SpringerLink
Log in

ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma

  • Article
  • Published:
Cancer Gene Therapy Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Cell types in six UTUC samples and one adjacent tissue sample were identified by scRNA-seq.
Fig. 2: Heterogeneity analysis of epithelial cells.
Fig. 3: Trajectory analysis and CNV of epithelial cells.
Fig. 4: Heterogeneity analysis of fibroblasts in the TME.
Fig. 5: Heterogeneity analysis of endothelial cells in the TME of UTUC.
Fig. 6: Heterogeneity analysis of T cells in the TME of UTUC.
Fig. 7: Heterogeneity analysis of B cells in the TME of UTUC.
Fig. 8: Heterogeneity analysis of myeloid cells in the TME of UTUC.
Fig. 9: Cell-to-cell communication in UTUC.

Similar content being viewed by others

Data availability

The data used to support the findings of this study are available from the corresponding authors upon request.

Code availability

The code used to support the findings of this study is available upon request from the corresponding author.

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33. https://doi.org/10.3322/caac.21708.

    Article  PubMed  Google Scholar 

  2. Hassler MR, Bray F, Catto JWF, Grollman AP, Hartmann A, Margulis V, et al. 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 :209–20. https://doi.org/10.1016/j.eururo.2020.05.039.

    Article  CAS  PubMed  Google Scholar 

  3. Crivelli JJ, Xylinas E, Kluth LA, Rieken M, Rink M, Shariat SF. Effect of smoking on outcomes of urothelial carcinoma: a systematic review of the literature. Eur Urol. 2014;65:742–54. https://doi.org/10.1016/j.eururo.2013.06.010.

    Article  CAS  PubMed  Google Scholar 

  4. Van Osch FH, Jochems SH, van Schooten FJ, Bryan RT, Zeegers MP. Significant role of lifetime cigarette smoking in worsening bladder cancer and upper tract urothelial carcinoma prognosis: a meta-analysis. J Urol. 2016;195:872–9. https://doi.org/10.1016/j.juro.2015.10.139.

    Article  PubMed  Google Scholar 

  5. Rouprêt M, Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, et al. European Association of Urology Guidelines on upper urinary tract urothelial carcinoma: 2020 update. Eur Urol. 2021;79:62–79. https://doi.org/10.1016/j.eururo.2020.05.042.

    Article  CAS  PubMed  Google Scholar 

  6. Laplane L, Duluc D, Bikfalvi A, Larmonier N, Pradeu T. Beyond the tumour microenvironment [published correction appears in Int J Cancer. 2021 Mar 15;148(6):E5]. Int J Cancer. 2019;145:2611–8. https://doi.org/10.1002/ijc.32343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Huang C, Bruggeman LA, Hydo LM, Miller RT. Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes. Exp Cell Res. 2012;318:1075–85. https://doi.org/10.1016/j.yexcr.2012.03.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ahn S, Park H. XIAP is essential for shear stress-enhanced Tyr-576 phosphorylation of FAK. Biochem Biophys Res Commun. 2010;399:256–61. https://doi.org/10.1016/j.bbrc.2010.07.064.

    Article  CAS  PubMed  Google Scholar 

  9. McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168:613–28. https://doi.org/10.1016/j.cell.2017.01.018.

    Article  CAS  PubMed  Google Scholar 

  10. McGranahan N, Swanton C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell. 2015;27:15–26. https://doi.org/10.1016/j.ccell.2014.12.001.

    Article  CAS  PubMed  Google Scholar 

  11. Blanpain C. Tracing the cellular origin of cancer. Nat Cell Biol. 2013;15:126–34. https://doi.org/10.1038/ncb2657.

    Article  CAS  PubMed  Google Scholar 

  12. Lourenco AR, Ban Y, Crowley MJ, Lee SB, Ramchandani D, Du W, et al. Differential contributions of pre- and post-EMT tumor cells in breast cancer metastasis. Cancer Res. 2020;80:163–9. https://doi.org/10.1158/0008-5472.CAN-19-1427.

    Article  CAS  PubMed  Google Scholar 

  13. Davis RT, Blake K, Ma D, Gabra MBI, Hernandez GA, Phung AT, et al. Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing. Nat Cell Biol. 2020;22:310–20. https://doi.org/10.1038/s41556-020-0477-0.

    Article  CAS  PubMed  Google Scholar 

  14. Müller M, Bird TG, Nault JC. The landscape of gene mutations in cirrhosis and hepatocellular carcinoma. J Hepatol. 2020;72:990–1002. https://doi.org/10.1016/j.jhep.2020.01.019.

    Article  CAS  PubMed  Google Scholar 

  15. Rebouissou S, Nault JC. Advances in molecular classification and precision oncology in hepatocellular carcinoma. J Hepatol. 2020;72:215–29. https://doi.org/10.1016/j.jhep.2019.08.017.

    Article  CAS  PubMed  Google Scholar 

  16. Baslan T, Hicks J. Unravelling biology and shifting paradigms in cancer with single-cell sequencing. Nat Rev Cancer. 2017;17:557–69. https://doi.org/10.1038/nrc.2017.58.

    Article  CAS  PubMed  Google Scholar 

  17. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, et al. Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014;344:1396–401. https://doi.org/10.1126/science.1254257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Albini A, Sporn MB. The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer. 2007;7:139–47. https://doi.org/10.1038/nrc2067.

    Article  CAS  PubMed  Google Scholar 

  19. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423–37. https://doi.org/10.1038/nm.3394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hosein AN, Huang H, Wang Z, Parmar K, Du W, Huang J, et al. Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution. JCI Insight. 2019;5:e129212. https://doi.org/10.1172/jci.insight.129212.

    Article  PubMed  Google Scholar 

  21. Wirtz D, Konstantopoulos K, Searson PC. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer. 2011;11:512–22. https://doi.org/10.1038/nrc3080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Turajlic S, Swanton C. Metastasis as an evolutionary process. Science. 2016;352:169–75. https://doi.org/10.1126/science.aaf2784.

    Article  CAS  PubMed  Google Scholar 

  23. Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet. 2003;33:49–54. https://doi.org/10.1038/ng1060.

    Article  CAS  PubMed  Google Scholar 

  24. Chen YC, Sahoo S, Brien R, Jung S, Humphries B, Lee W, et al. Single-cell RNA-sequencing of migratory breast cancer cells: discovering genes associated with cancer metastasis. Analyst. 2019;144:7296–309. https://doi.org/10.1039/c9an01358j.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kim KT, Lee HW, Lee HO, Song HJ, Jeong da E, Shin S, et al. Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma. Genome Biol. 2016;17:80. https://doi.org/10.1186/s13059-016-0945-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ, et al. An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell. 2019;178:835–49.e21. https://doi.org/10.1016/j.cell.2019.06.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liang Y, Tan Y, Guan B, Guo B, **a M, Li J, et al. Single-cell atlases link macrophages and CD8+ T-cell subpopulations to disease progression and immunotherapy response in urothelial carcinoma. Theranostics. 2022;12:7745–59. https://doi.org/10.7150/thno.77281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582–98. https://doi.org/10.1038/nrc.2016.73.

    Article  CAS  PubMed  Google Scholar 

  29. Ajani JA, Wang X, Song S, Suzuki A, Taketa T, Sudo K, et al. ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients. Mol Oncol. 2014;8:142–9. https://doi.org/10.1016/j.molonc.2013.10.007.

    Article  CAS  PubMed  Google Scholar 

  30. Patterson LH, Murray GI. Tumour cytochrome P450 and drug activation. Curr Pharm Des. 2002;8:1335–47. https://doi.org/10.2174/1381612023394502.

    Article  CAS  PubMed  Google Scholar 

  31. Casazza A, Laoui D, Wenes M, Rizzolio S, Bassani N, Mambretti M, et al. Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity. Cancer Cell. 2013;24:695–709. https://doi.org/10.1016/j.ccr.2013.11.007.

    Article  CAS  PubMed  Google Scholar 

  32. Tanaka K, Arao T, Maegawa M, Matsumoto K, Kaneda H, Kudo K, et al. SRPX2 is overexpressed in gastric cancer and promotes cellular migration and adhesion. Int J Cancer. 2009;124:1072–80. https://doi.org/10.1002/ijc.24065.

    Article  CAS  PubMed  Google Scholar 

  33. Liu KL, Wu J, Zhou Y, Fan JH. Increased Sushi repeat-containing protein X-linked 2 is associated with progression of colorectal cancer. Med Oncol. 2015;32:99. https://doi.org/10.1007/s12032-015-0548-4.

    Article  CAS  PubMed  Google Scholar 

  34. Gao Z, Zhang J, Bi M, Han X, Han Z, Wang H, et al. SRPX2 promotes cell migration and invasion via FAK dependent pathway in pancreatic cancer. Int J Clin Exp Pathol. 2015;8:4791–8.

    PubMed  PubMed Central  Google Scholar 

  35. Tang H, Zhao J, Zhang L, Zhao J, Zhuang Y, Liang P. SRPX2 enhances the epithelial-mesenchymal transition and temozolomide resistance in glioblastoma cells. Cell Mol Neurobiol. 2016;36:1067–76. https://doi.org/10.1007/s10571-015-0300-9.

    Article  CAS  PubMed  Google Scholar 

  36. Horie M, Saito A, Yamaguchi Y, Ohshima M, Nagase T. Three-dimensional Co-culture model for tumor-stromal interaction. J Vis Exp. 2015;96:52469. https://doi.org/10.3791/52469.

    Article  Google Scholar 

  37. Gonzalez-Zubeldia I, Dotor J, Redrado M, Bleau AM, Manrique I, de Aberasturi AL, et al. Co-migration of colon cancer cells and CAFs induced by TGFβ1 enhances liver metastasis. Cell Tissue Res. 2015;359:829–39. https://doi.org/10.1007/s00441-014-2075-6.

    Article  CAS  PubMed  Google Scholar 

  38. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321–30. https://doi.org/10.1038/nature21349.

    Article  CAS  PubMed  Google Scholar 

  39. Smeland S, Bielack SS, Whelan J, Bernstein M, Hogendoorn P, Krailo MD, et al. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. Eur J Cancer. 2019;109:36–50. https://doi.org/10.1016/j.ejca.2018.11.027.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Harris RJ, Cheung A, Ng JCF, Laddach R, Chenoweth AM, Crescioli S, et al. Tumor-infiltrating B lymphocyte profiling identifies IgG-biased, clonally expanded prognostic phenotypes in triple-negative breast cancer. Cancer Res. 2021;81:4290–304. https://doi.org/10.1158/0008-5472.CAN-20-3773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Magerus A, Bercher-Brayer C, Rieux-Laucat F. The genetic landscape of the FAS pathway deficiencies. Biomed J. 2021;44:388–99. https://doi.org/10.1016/j.bj.2021.06.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vonderheide RH. CD40 agonist antibodies in cancer immunotherapy. Annu Rev Med. 2020;71:47–58. https://doi.org/10.1146/annurev-med-062518-045435.

    Article  CAS  PubMed  Google Scholar 

  43. Brantley-Sieders DM, Caughron J, Hicks D, Pozzi A, Ruiz JC, Chen J. EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci. 2004;117:2037–49. https://doi.org/10.1242/jcs.01061.

    Article  CAS  PubMed  Google Scholar 

  44. Stewart GD, Bariol SV, Grigor KM, Tolley DA, McNeill SA. A comparison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract. BJU Int. 2005;95:791–3. https://doi.org/10.1111/j.1464-410X.2005.05402.x.

    Article  PubMed  Google Scholar 

  45. Cha EK, Shariat SF, Kormaksson M, Novara G, Chromecki TF, Scherr DS, et al. Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. Eur Urol. 2012;61:818–25. https://doi.org/10.1016/j.eururo.2012.01.021.

    Article  PubMed  Google Scholar 

  46. Sobierajska K, Ciszewski WM, Sacewicz-Hofman I, Niewiarowska J. Endothelial cells in the tumor microenvironment. Adv Exp Med Biol. 2020;1234:71–86. https://doi.org/10.1007/978-3-030-37184-5_6.

    Article  CAS  PubMed  Google Scholar 

  47. Kuzet SE, Gaggioli C. Fibroblast activation in cancer: when seed fertilizes soil. Cell Tissue Res. 2016;365:607–19. https://doi.org/10.1007/s00441-016-2467-x.

    Article  CAS  PubMed  Google Scholar 

  48. Dong D, Yao Y, Song J, Sun L, Zhang G. Cancer-associated fibroblasts regulate bladder cancer invasion and metabolic phenotypes through autophagy. Dis Markers. 2021;2021:6645220 https://doi.org/10.1155/2021/6645220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen Z, Zhou L, Liu L, Hou Y, **ong M, Yang Y, et al. Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma. Nat Commun. 2020;11:5077. https://doi.org/10.1038/s41467-020-18916-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Liu B, Pan S, Liu J, Kong C. Cancer-associated fibroblasts and the related Runt-related transcription factor 2 (RUNX2) promote bladder cancer progression. Gene. 2021;775:145451. https://doi.org/10.1016/j.gene.2021.145451.

    Article  CAS  PubMed  Google Scholar 

  51. Chung W, Eum HH, Lee HO, Lee KM, Lee HB, Kim KT, et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer. Nat Commun. 2017;8:15081 https://doi.org/10.1038/ncomms15081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. **a W, Zhang S, Duan H, Wang C, Qian S, Shen H. The combination therapy of Everolimus and anti-PD-1 improves the antitumor effect by regulating CD8+ T cells in bladder cancer. Med Oncol. 2022;39:37. https://doi.org/10.1007/s12032-021-01624-5.

    Article  CAS  PubMed  Google Scholar 

  53. Oh DY, Kwek SS, Raju SS, Li T, McCarthy E, Chow E, et al. Intratumoral CD4+ T cells mediate anti-tumor cytotoxicity in human bladder cancer. Cell. 2020;181:1612–25.e13. https://doi.org/10.1016/j.cell.2020.05.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Horn T, Laus J, Seitz AK, Maurer T, Schmid SC, Wolf P, et al. The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer. World J Urol. 2016;34:181–7. https://doi.org/10.1007/s00345-015-1615-3.

    Article  CAS  PubMed  Google Scholar 

  55. Wang T, Zhou Q, Zeng H, Zhang H, Liu Z, Shao J, et al. CCR8 blockade primes anti-tumor immunity through intratumoral regulatory T cells destabilization in muscle-invasive bladder cancer. Cancer Immunol Immunother. 2020;69:1855–67. https://doi.org/10.1007/s00262-020-02583-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Winerdal ME, Krantz D, Hartana CA, Zirakzadeh AA, Linton L, Bergman EA, et al. Urinary bladder cancer tregs suppress MMP2 and potentially regulate invasiveness. Cancer Immunol Res. 2018;6:528–38. https://doi.org/10.1158/2326-6066.CIR-17-0466.

    Article  CAS  PubMed  Google Scholar 

  57. Goc J, Germain C, Vo-Bourgais TK, Lupo A, Klein C, Knockaert S, et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res. 2014;74:705–15. https://doi.org/10.1158/0008-5472.CAN-13-1342.

    Article  CAS  PubMed  Google Scholar 

  58. Nazarkina ZhK, Laktionov PP. [Preparation of dendritic cells for cancer immunotherapy]. Biomed Khim. 2015;61:30–40. https://doi.org/10.18097/pbmc20156101030.

    Article  CAS  PubMed  Google Scholar 

  59. Laoui D, Keirsse J, Morias Y, Van Overmeire E, Geeraerts X, Elkrim Y, et al. The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity. Nat Commun. 2016;7:13720. https://doi.org/10.1038/ncomms13720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (Grant Nos.: 81972409 and 81672549) and the Medical Science and Technology Project of Henan Province in 2019 (Grant No.: LHGJ20190567) and 2020 (Grant No.: LHGJ20200582).

Author information

Author notes

  1. These authors contributed equally: Shiyong **n, Yanwei Zhang, Zhenhua Zhang.

Authors and Affiliations

  1. Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China

    Shiyong **n, Yanwei Zhang, Ziyao Li, **anchao Sun, **ang Liu, Liang **, Weiyi Li, Chaozhi Tang, Wangli Mei, Zhen Zhou, Rongbing Li, **aofei Wen, Guosheng Yang, Weihua Chen & Lin Ye

  2. Department of Urology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471000, China

    Shiyong **n

  3. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China

    Zhenhua Zhang

  4. Department of Pathology, The Third Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China

    Qiong Cao

  5. Department of Central Laboratory, Zhengzhou University, Luoyang Central Hospital, Luoyang, 471003, China

    Haojie Wang

  6. Department of Pathology, Yiluo Hospital of Luoyang, The Teaching Hospital of Henan University of Science and Technology, Luoyang, China

    Zhihao Wei

  7. Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Junhua Zheng

Authors
  1. Shiyong **n
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanwei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhenhua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ziyao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. **anchao Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. **ang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liang **
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Weiyi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chaozhi Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wangli Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qiong Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Haojie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Zhihao Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Zhen Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Rongbing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. **aofei Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Guosheng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Weihua Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Junhua Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Lin Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Lin Ye designed the research methods. Shiyong **n, Zhenhua Zhang, and **anchao Sun performed the analysis. Liang ** and Weiyi Li analyzed the data. Shiyong **n drafted and revised the manuscript. All authors approved the final version of the submitted manuscript and agreed to be responsible for all aspects of the work.

Corresponding authors

Correspondence to Weihua Chen, Junhua Zheng or Lin Ye.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

**n, S., Zhang, Y., Zhang, Z. et al. ScRNA-seq revealed the tumor microenvironment heterogeneity related to the occurrence and metastasis in upper urinary tract urothelial carcinoma. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00779-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41417-024-00779-3

  • Springer Nature America, Inc.

Search

Navigation