Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer
| Autor: | Xin Wei, Xiu-zhen Wu, Yi Wang, Jun Qin, Xiao-Tian Ni, Kai Li, Jing-Ying Zhang, Gaohaer Kadeerhan, Lin-Heng Wang, Xue Li, Nairen Zheng, Mingwei Liu, Lan-fu Zhang, Sha Huang, Jian-Ming Xu, Wei-Dong Liu, Wen-Qing Li, Zhongwu Li, Zong-Chao Liu, Wei-Cheng You, Markus Gerhard, Tong Zhou, Yang Zhang, Kai-Feng Pan, Jin Dai, Zhe-Xuan Li, Fan Hua, Wen-Hui Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Proteomics medicine.medical_specialty China Medicine (General) Population Precancerous gastric lesions General Biochemistry Genetics and Molecular Biology R5-920 Stomach Neoplasms Tandem Mass Spectrometry Internal medicine medicine Humans Prospective Studies Stage (cooking) education Original Research education.field_of_study Proteomic Profiling business.industry General Medicine Biomarker Early Gastric Cancer Biomarker (cell) Case-Control Studies Disease Progression Immunohistochemistry Medicine business Gastric cancer Precancerous Conditions Cohort study Chromatography Liquid |
| Zdroj: | EBioMedicine, Vol 74, Iss, Pp 103714-(2021) EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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