Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer

Han, Xiaoyang; Gao, Yan; Jiang, Mei; Li, Zhefeng; Guo, Jiahao; Li, Yue; Yi, Junjie; Hou, Lisha; Cheng, Jin; Feng, Lei; Jin, Yulan; Zhao, Xiaoting; Yue, Wentao

doi:10.7150/jca.95269



International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

Nanotheranostics

Global reach, higher impact

Full Text | PDF

J Cancer 2024; 15(11):3427-3440. doi:10.7150/jca.95269 This issue Cite

Research Paper

Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer

Xiaoyang Han¹, Yan Gao¹, Mei Jiang¹, Zhefeng Li¹, Jiahao Guo¹, Yue Li¹, Junjie Yi¹, Lisha Hou¹, Jin Cheng¹, Lei Feng¹, Yulan Jin^2✉, Xiaoting Zhao^1✉, Wentao Yue^1✉

1. Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.
2. Department of Pathology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.

Citation:

Han X, Gao Y, Jiang M, Li Z, Guo J, Li Y, Yi J, Hou L, Cheng J, Feng L, Jin Y, Zhao X, Yue W. Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer. J Cancer 2024; 15(11):3427-3440. doi:10.7150/jca.95269. https://www.jcancer.org/v15p3427.htm

Other styles

Abstract

Purpose: Platinum-based chemotherapy is effective but limited by resistance in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) can reveal tumour cell heterogeneity and subclonal differentiation. We aimed to analyze resistance mechanisms and potential targets in HGSOC using scRNA-seq.

Methods: We performed 10× genomics scRNA-seq sequencing on tumour tissues from 3 platinum-sensitive and 3 platinum-resistant HGSOC patients. We analyzed cell subcluster communication networks and spatial distribution using cellchat. We performed RNA-seq analysis on TACSTD2, a representative resistance gene in the E0 subcluster, to explore its molecular mechanism.

Results: Epithelial cells, characterized by distinct chemotherapy resistance traits and highest gene copy number variations, revealed a specific cisplatin-resistant cluster (E0) associated with poor prognosis. E0 exhibited malignant features related to resistance, fostering growth through communication with fibroblasts and endothelial cells. Spatially, E0 promoted fibroblasts to protect tumour cells and impede immune cells infiltration. Furthermore, TACSTD2 was identified as a representative gene of the E0 subcluster, elucidating its role in platinum resistance through the Rap1/PI3K/AKT pathway.

Conclusions: Our study reveals a platinum-resistant epithelial cell subcluster E0 and its association with TACSTD2 in HGSOC, uncovers new insights and evidence for the platinum resistance mechanism, and provides new ideas and targets for the development of therapeutic strategies against TACSTD2+ epithelial cancer cells.

Keywords: ovarian cancer, platinum resistance, TACSTD2, prognosis, scRNA-seq

Citation styles

APA

Han, X., Gao, Y., Jiang, M., Li, Z., Guo, J., Li, Y., Yi, J., Hou, L., Cheng, J., Feng, L., Jin, Y., Zhao, X., Yue, W. (2024). Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer. Journal of Cancer, 15(11), 3427-3440. https://doi.org/10.7150/jca.95269.

ACS

Han, X.; Gao, Y.; Jiang, M.; Li, Z.; Guo, J.; Li, Y.; Yi, J.; Hou, L.; Cheng, J.; Feng, L.; Jin, Y.; Zhao, X.; Yue, W. Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer. J. Cancer 2024, 15 (11), 3427-3440. DOI: 10.7150/jca.95269.

NLM

CSE

Han X, Gao Y, Jiang M, Li Z, Guo J, Li Y, Yi J, Hou L, Cheng J, Feng L, Jin Y, Zhao X, Yue W. 2024. Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer. J Cancer. 15(11):3427-3440.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.