Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. Methods: We portrayed proteomic landscape and explored proteomic signatures associated...

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Autores principales:	Xue Li, Nai-Ren Zheng, Lin-Heng Wang, Zhong-Wu Li, Zong-Chao Liu, Hua Fan, Yi Wang, Jin Dai, Xiao-Tian Ni, Xin Wei, Ming-Wei Liu, Kai Li, Zhe-Xuan Li, Tong Zhou, Yang Zhang, Jing-Ying Zhang, Gaohaer Kadeerhan, Sha Huang, Wen-Hui Wu, Wei-Dong Liu, Xiu-Zhen Wu, Lan-Fu Zhang, Jian-Ming Xu, Markus Gerhard, Wei-Cheng You, Kai-Feng Pan, Wen-Qing Li, Jun Qin
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Proteomics Precancerous gastric lesions Gastric cancer Biomarker Medicine R Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9b4b3088f0d348368c3f1b99b54ae4de
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spelling	oai:doaj.org-article:9b4b3088f0d348368c3f1b99b54ae4de2021-11-24T04:32:01ZProteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer2352-396410.1016/j.ebiom.2021.103714https://doaj.org/article/9b4b3088f0d348368c3f1b99b54ae4de2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352396421005089https://doaj.org/toc/2352-3964Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280–473 days), and an independent case-control study from Beijing (n = 99). Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78–0.99) vs. 0.56 (0.36–0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. Funding: The funders are listed in the Acknowledgement.Xue LiNai-Ren ZhengLin-Heng WangZhong-Wu LiZong-Chao LiuHua FanYi WangJin DaiXiao-Tian NiXin WeiMing-Wei LiuKai LiZhe-Xuan LiTong ZhouYang ZhangJing-Ying ZhangGaohaer KadeerhanSha HuangWen-Hui WuWei-Dong LiuXiu-Zhen WuLan-Fu ZhangJian-Ming XuMarkus GerhardWei-Cheng YouKai-Feng PanWen-Qing LiJun QinElsevierarticleProteomicsPrecancerous gastric lesionsGastric cancerBiomarkerMedicineRMedicine (General)R5-920ENEBioMedicine, Vol 74, Iss , Pp 103714- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Proteomics Precancerous gastric lesions Gastric cancer Biomarker Medicine R Medicine (General) R5-920
spellingShingle	Proteomics Precancerous gastric lesions Gastric cancer Biomarker Medicine R Medicine (General) R5-920 Xue Li Nai-Ren Zheng Lin-Heng Wang Zhong-Wu Li Zong-Chao Liu Hua Fan Yi Wang Jin Dai Xiao-Tian Ni Xin Wei Ming-Wei Liu Kai Li Zhe-Xuan Li Tong Zhou Yang Zhang Jing-Ying Zhang Gaohaer Kadeerhan Sha Huang Wen-Hui Wu Wei-Dong Liu Xiu-Zhen Wu Lan-Fu Zhang Jian-Ming Xu Markus Gerhard Wei-Cheng You Kai-Feng Pan Wen-Qing Li Jun Qin Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
description	Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280–473 days), and an independent case-control study from Beijing (n = 99). Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78–0.99) vs. 0.56 (0.36–0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. Funding: The funders are listed in the Acknowledgement.
format	article
author	Xue Li Nai-Ren Zheng Lin-Heng Wang Zhong-Wu Li Zong-Chao Liu Hua Fan Yi Wang Jin Dai Xiao-Tian Ni Xin Wei Ming-Wei Liu Kai Li Zhe-Xuan Li Tong Zhou Yang Zhang Jing-Ying Zhang Gaohaer Kadeerhan Sha Huang Wen-Hui Wu Wei-Dong Liu Xiu-Zhen Wu Lan-Fu Zhang Jian-Ming Xu Markus Gerhard Wei-Cheng You Kai-Feng Pan Wen-Qing Li Jun Qin
author_facet	Xue Li Nai-Ren Zheng Lin-Heng Wang Zhong-Wu Li Zong-Chao Liu Hua Fan Yi Wang Jin Dai Xiao-Tian Ni Xin Wei Ming-Wei Liu Kai Li Zhe-Xuan Li Tong Zhou Yang Zhang Jing-Ying Zhang Gaohaer Kadeerhan Sha Huang Wen-Hui Wu Wei-Dong Liu Xiu-Zhen Wu Lan-Fu Zhang Jian-Ming Xu Markus Gerhard Wei-Cheng You Kai-Feng Pan Wen-Qing Li Jun Qin
author_sort	Xue Li
title	Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
title_short	Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
title_full	Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
title_fullStr	Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
title_full_unstemmed	Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
title_sort	proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/9b4b3088f0d348368c3f1b99b54ae4de
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Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer

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