Single-Exosome Profiling Identifies ITGB3+and ITGAM plus Exosome Subpopulations as Promising Early Diagnostic Biomarkers and Therapeutic Targets for Colorectal Cancer

Guo, Wei1; Cai, Yanling1,2,3; Liu, Xianming4; Ji, Yuge1; Zhang, Cuiyu1; Wang, Liyan5; Liao, Wenting6; Liu, Yuefei6; Cui, Nan6; Xiang, Jinsheng6; Li, Zesong2,3; Wu, Di6,7; Li, Jingxin1

2023-01-30

10.34133/research.0041

RESEARCH   Impact Factor & Quartile

2096-5168

2639-5274

Tumor metastasis is a hallmark of colorectal cancer (CRC), in which exosome plays a crucial role with its function in intercellular communication. Plasma exosomes were collected from healthy control (HC) donors, localized primary CRC and liver-metastatic CRC patients. We performed proximity barcoding assay (PBA) for single-exosome analysis, which enabled us to identify the alteration in exosome subpopulations associated with CRC progression. By in vitro and in vivo experiments, the biological impact of these subpopulations on cancer proliferation, migration, invasion, and metastasis was investigated. The potential application of exosomes as diagnostic biomarkers was evaluated in 2 independent validation cohorts by PBA. Twelve distinct exosome subpopulations were determined. We found 2 distinctly abundant subpopulations: one ITGB3-positive and the other ITGAM-positive. The ITGB3-positive cluster is rich in liver-metastatic CRC, compared to both HC group and primary CRC group. On the contrary, ITGAM-positive exosomes show a large-scale increase in plasma of HC group, compared to both primary CRC and metastatic CRC groups. Notably, both discovery cohort and validation cohort verified ITGB3+ exosomes as potential diagnostic biomarker. ITGB3+ exosomes promote proliferation, migration, and invasion capability of CRC. In contrast, ITGAM+ exosomes suppress CRC development. Moreover, we also provide evidence that one of the sources of ITGAM+ exosomes is macrophage. ITGB3+ exosomes and ITGAM+ exosomes are proven 2 potential diagnostic, prognostic, and therapeutic biomarkers for management of CRC.

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English

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National Natural Science Foundation of China["82000779","31971061"] ; Taishan Pandeng Scholar Program of Shandong Province[tspd20210321]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000992010200002

AMER ASSOC ADVANCEMENT SCIENCE

Web of Science

1.Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Sch Basic Med Sci,Dept Physiol,Dept Colorectal Sur, Jinan 250012, Shandong, Peoples R China
2.Shenzhen Univ, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen Inst Translat Med,Dept Urol,Guangdong Pro, Shenzhen 518035, Peoples R China
3.Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen Inst Translat Med,Shenzhen Key Lab Genito, Shenzhen 518035, Peoples R China
4.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Dept Gastrointestinal Surg,Clin, Shenzhen 518020, Guangdong, Peoples R China
5.Shandong Univ, Ctr Expt Nucl Med & Elect Microscope, Sch Basic Med Sci, Jinan 250012, Shandong, Peoples R China
6.Shenzhen SecreTech Co Ltd, Shenzhen, Peoples R China
7.Vesicode AB, Nobelsvag 16, Solna, Sweden

Guo, Wei,Cai, Yanling,Liu, Xianming,et al. Single-Exosome Profiling Identifies ITGB3+and ITGAM plus Exosome Subpopulations as Promising Early Diagnostic Biomarkers and Therapeutic Targets for Colorectal Cancer[J]. RESEARCH,2023,6.

Guo, Wei.,Cai, Yanling.,Liu, Xianming.,Ji, Yuge.,Zhang, Cuiyu.,...&Li, Jingxin.(2023).Single-Exosome Profiling Identifies ITGB3+and ITGAM plus Exosome Subpopulations as Promising Early Diagnostic Biomarkers and Therapeutic Targets for Colorectal Cancer.RESEARCH,6.

Guo, Wei,et al."Single-Exosome Profiling Identifies ITGB3+and ITGAM plus Exosome Subpopulations as Promising Early Diagnostic Biomarkers and Therapeutic Targets for Colorectal Cancer".RESEARCH 6(2023).