An integrated analysis of bulk and single-cell sequencing data reveals that EMP1+/COL3A1+ fibroblasts contribute to the bone metastasis process in breast, prostate, and renal cancers

Haoyuan Du; Hua Wang; Yuwei Luo; Yang Jiao; Jiajun Wu; Shaowei Dong; Dong Du

doi:10.3389/fimmu.2023.1313536

An integrated analysis of bulk and single-cell sequencing data reveals that EMP1⁺/COL3A1⁺ fibroblasts contribute to the bone metastasis process in breast, prostate, and renal cancers

Front Immunol. 2023 Dec 19:14:1313536. doi: 10.3389/fimmu.2023.1313536. eCollection 2023.

Authors

Haoyuan Du¹, Hua Wang¹, Yuwei Luo², Yang Jiao³, Jiajun Wu⁴, Shaowei Dong⁴, Dong Du⁵

Affiliations

¹ Department of Orthopedics and Joints, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
² Department of Breast Surgery, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
³ Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
⁴ Department of Pediatric Research, Shenzhen Children's Hospital, Shenzhen, Guangdong, China.
⁵ Department of Health Management, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.

Abstract

Introduction: Bone metastasis (BoM) occurs when cancer cells spread from their primary sites to a bone. Currently, the mechanism underlying this metastasis process remains unclear.

Methods: In this project, through an integrated analysis of bulk-sequencing and single-cell RNA transcriptomic data, we explored the BoM-related features in tumor microenvironments of different tumors.

Results: We first identified 34 up-regulated genes during the BoM process in breast cancer, and further explored their expression status among different components in the tumor microenvironment (TME) of BoM samples. Enriched EMP1+ fibroblasts were found in BoM samples, and a COL3A1-ADGRG1 communication between these fibroblasts and cancer cells was identified which might facilitate the BoM process. Moreover, a significant correlation between EMP1 and COL3A1 was identified in these fibroblasts, confirming the potential connection of these genes during the BoM process. Furthermore, the existence of these EMP1+/COL3A1+ fibroblasts was also verified in prostate cancer and renal cancer BoM samples, suggesting the importance of these fibroblasts from a pan-cancer perspective.

Discussion: This study is the first attempt to investigate the relationship between fibroblasts and BoM process across multi-tumor TMEs. Our findings contribute another perspective in the exploration of BoM mechanism while providing some potential targets for future treatments of tumor metastasis.

Keywords: EMP1+/COL3A1+ fibroblasts; bone metastasis; combined analysis; multi-tumor TMEs; scRNAseq.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Neoplasms* / genetics
Carcinoma, Renal Cell*
Collagen Type III
Fibroblasts
Humans
Kidney Neoplasms* / genetics
Male
Melanoma*
Neoplasms, Second Primary*
Prostate
Skin Neoplasms*
Tumor Microenvironment / genetics

Substances

COL3A1 protein, human
Collagen Type III

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (32000465 to SD).