Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Li X

PROVIDER: S-EPMC8617343 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Li Xue X Zheng Nai-Ren NR Wang Lin-Heng LH Li Zhong-Wu ZW Liu Zong-Chao ZC Fan Hua H Wang Yi Y Dai Jin J Ni Xiao-Tian XT Wei Xin X Liu Ming-Wei MW Li Kai K Li Zhe-Xuan ZX Zhou Tong T Zhang Yang Y Zhang Jing-Ying JY Kadeerhan Gaohaer G Huang Sha S Wu Wen-Hui WH Liu Wei-Dong WD Wu Xiu-Zhen XZ Zhang Lan-Fu LF Xu Jian-Ming JM Gerhard Markus M You Wei-Cheng WC Pan Kai-Feng KF Li Wen-Qing WQ Qin Jun J

EBioMedicine 20211122

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 34818622

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Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

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