Effect of fibroblast heterogeneity on prognosis and drug resistance in high-grade serous ovarian cancer

Tingjie Wang ^1,2, Lingxi Tian ³, Bing Wei ^1,2

¹Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China.
²Henan Key Laboratory of Molecular Pathology, Zhengzhou, People's Republic of China.
³MOE Key Laboratory of Intelligent Biomanufacturing, School of Bioengineering, Dalian University of Technology, Dalian, 116024, People's Republic of China.
⁴School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
⁵Department of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, People's Republic of China.
⁶Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, School of Medical Technology, Xinxiang Medical University, Xinxiang, People's Republic of China.
⁷Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
⁸MOE Key Laboratory of Intelligent Biomanufacturing, School of Bioengineering, Dalian University of Technology, Dalian, 116024, People's Republic of China. junyang@dlut.edu.cn.
⁹Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China. yongjunguo@hotmail.com.
¹⁰Henan Key Laboratory of Molecular Pathology, Zhengzhou, People's Republic of China. yongjunguo@hotmail.com.

⁰Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China.

Scientific Reports +

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November 4, 2024

View abstract on PubMed

Summary

Tumor heterogeneity in high-grade serous ovarian cancer (HGSOC) impacts prognosis and treatment. Increased functional clonality and CXCL12-positive fibroblasts correlate with poor outcomes and chemotherapy resistance.

Area Of Science

Oncology
Genomics
Cancer Biology

Background

Tumor heterogeneity significantly impacts high-grade serous ovarian cancer (HGSOC) prognosis and therapeutic efficacy.
Understanding intra- and intertumoral heterogeneity is crucial for developing effective treatment strategies.

Purpose Of The Study

To analyze tumor evolution and heterogeneity in HGSOC using single-cell and spatial transcriptomics.
To investigate the correlation between tumor heterogeneity, prognosis, and chemotherapy response in HGSOC patients.

Main Methods

Utilized tumor evolution analysis on single-cell transcriptomic data from 28 HGSOC patients.
Developed a machine-learning approach to deconstruct tumor cell evolutionary patterns.
Validated findings using spatial and bulk transcriptomic data from 1,030 patients.

Main Results

Increased tumor cell state heterogeneity strongly correlates with patient prognosis and treatment response.
Intra- and intertumoral functional clonality are associated with cancer-associated fibroblasts (CAFs).
Spatial proximity of CXCL12-positive CAFs and tumor cells correlates with poor prognosis and chemotherapy resistance.

Conclusions

Tumor heterogeneity and specific fibroblast interactions are key drivers of HGSOC progression and treatment failure.
A 24-gene panel predicting prognosis and chemotherapy response based on CXCL12-positive fibroblasts was developed.
Insights into tumor cell community behavior and evolution offer potential therapeutic targets for HGSOC.

Keywords:

CXCL12 HGSOC Tumor cell state cancer-associated fibroblasts functional clonality microenvironment spatiotemporal transcriptome tumor evolution tumor transcriptomic heterogeneity

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