Identification and validation of the surface proteins FIBG, PDGF-β, and TGF-β on serum extracellular vesicles for non-invasive detection of colorectal cancer: experimental study

Huang, Zhijian1,2; Deng, Cuncan2; Ma, Caiqi6; He, Guirong3,4; Tao, Jian3,4; Zhang, Lijun3,4; Hu, Xiaoyun3,4; Mo, Yanfang3,4; Qiu, Lumei3,4; Zhang, Ningfang3,4; Luo, Chuanghua8; Xing, Shan7; Xie, Jinye5; Yin, Haofan2,3,4

2024-08-01

10.1097/JS9.0000000000001533

INTERNATIONAL JOURNAL OF SURGERY   影响因子和分区

1743-9191

1743-9159

Objectives:The absence of non-invasive biomarkers for the early diagnosis of colorectal cancer (CRC) has contributed to poor prognosis. Extracellular vesicles (EVs) have emerged as promising candidates for cancer monitoring using liquid biopsy. However, the complexity of EVs isolation procedures and the absence of clear targets for detecting serum-derived EVs have hindered the clinical application of EVs in early CRC diagnosis.Methods:In the discovery phase, we conducted a comprehensive 4D-DIA proteomic analysis of serum-derived EVs samples from 37 individuals, performing an initial screening of EVs surface proteins. In the technical validation phase, we developed an extraction-free CRC-EVArray microarray to assess the expression of these potential EVs surface proteins in a multi-centre study comprising 404 individuals. In the application phase, the authors evaluated the diagnostic efficacy of the CRC-EVArray model based on machine-learning algorithms.Results:Through 4D-DIA proteomic analysis, the authors identified seven potential EVs surface proteins showing significantly differential expression in CRC patients compared to healthy controls. Utilizing our developed high-throughput CRC-EVArray microarray, we further confirmed the differential expression of three EVs surface proteins, FIBG, PDGF-beta and TGF-beta, in a large sample population. Moreover, we established an optimal CRC-EVArray model using the NNET algorithm, demonstrating superior diagnostic efficacy with an area under the curve (AUC) of 0.882 in the train set and 0.937 in the test set. Additionally, we predicted the functions and potential origins of these EVs-derived proteins through a series of multi-omics approaches.Conclusions:Our systematic exploration of surface protein expression profiles on serum-derived EVs has identified FIBG, PDGF-beta, and TGF-beta as novel diagnostic biomarkers for CRC. The development of CRC-EVArray diagnostic model based on these findings provided an effective tool for the large-scale CRC screening, thus facilitating its translation into clinical practice.

Biomarker colorectal cancer extracellular vesicles machine-learning

SCI

英语

通讯

National Nature Science Foundation of China["82103346","82202829","82202985"] ; General project of Shenzhen Science and Technology Innovation Commission[JCYJ20220530145003008] ; Guangdong Basic and Applied Basic Research Foundation["2021A1515110094","2022A1515111199","2022A1515111062","2023A1515220107"]

Surgery

Surgery

WOS:001291410700119

LIPPINCOTT WILLIAMS & WILKINS

Web of Science

1.Sun Yat Sen Univ, Affiliated Hosp 7, Dept Pathol, Shenzhen, Peoples R China
2.Sun Yat sen Univ, Affiliated Hosp 7, Digest Dis Ctr, 628 Zhenyuan Rd, Shenzhen, Guangdong, Peoples R China
3.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Lab Med, Shenzhen, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Peoples R China
5.Zhongshan City Peoples Hosp, Dept Lab Med, 2 Sunwen East Rd, Zhongshan, Guangdong, Peoples R China
6.Guangzhou Med Univ, Affiliated Hosp 5, Dept Oncol, Key Lab Biol Targeting Diag Therapy & Rehabil Guan, Guangzhou, Guangdong, Peoples R China
7.Sun Yat sen Univ, Canc Ctr, Dept Clin Lab, State Key Lab Oncol South China, 651 Dongfeng East Rd, Guangzhou, Guangdong, Peoples R China
8.Sun Yat sen Univ, Collaborat Innovat Ctr Canc Med, Canc Ctr, State Key Lab Oncol South China, Guangzhou, Guangdong, Peoples R China

Huang, Zhijian,Deng, Cuncan,Ma, Caiqi,et al. Identification and validation of the surface proteins FIBG, PDGF-β, and TGF-β on serum extracellular vesicles for non-invasive detection of colorectal cancer: experimental study[J]. INTERNATIONAL JOURNAL OF SURGERY,2024,110(8).

Huang, Zhijian.,Deng, Cuncan.,Ma, Caiqi.,He, Guirong.,Tao, Jian.,...&Yin, Haofan.(2024).Identification and validation of the surface proteins FIBG, PDGF-β, and TGF-β on serum extracellular vesicles for non-invasive detection of colorectal cancer: experimental study.INTERNATIONAL JOURNAL OF SURGERY,110(8).

Huang, Zhijian,et al."Identification and validation of the surface proteins FIBG, PDGF-β, and TGF-β on serum extracellular vesicles for non-invasive detection of colorectal cancer: experimental study".INTERNATIONAL JOURNAL OF SURGERY 110.8(2024).