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

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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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.

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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.

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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).

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Lin Ye designed the research methods. Shiyong Xin, Zhenhua Zhang, and Xianchao Sun performed the analysis. Liang Jin and Weiyi Li analyzed the data. Shiyong Xin 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.

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Correspondence to Weihua Chen, Junhua Zheng or Lin Ye.

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Xin, 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

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