Identification of plasma proteomic signatures associated with the progression of cardia gastric cancer and precancerous lesions.

J Natl Cancer Cent

Office of National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Published: December 2023

AI Article Synopsis

  • Researchers developed a noninvasive diagnostic method using DIA proteomics to identify protein markers for cardia gastric cancer (CGC), as effective screening biomarkers are currently lacking.
  • Plasma samples from 40 individuals were analyzed, revealing distinct proteomic features among CGC, dysplasia types, and healthy controls, leading to the identification of potential biomarkers.
  • Three candidate proteins (GSTP1, CSRP1, and LY6G6F) demonstrated high accuracy in distinguishing CGC and precancerous lesions from healthy individuals, indicating the need for further validation and larger studies to explore clinical applications.

Article Abstract

Objective: Considering that there are no effective biomarkers for the screening of cardia gastric cancer (CGC), we developed a noninvasive diagnostic approach, employing data-independent acquisition (DIA) proteomics to identify candidate protein markers.

Methods: Plasma samples were obtained from 40 subjects, 10 each for CGC, cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD), and healthy controls. Proteomic profiles were obtained through liquid chromatography-mass spectrometry (LC-MS/MS-based DIA proteomics. Candidate plasma proteins were identified by weighted gene co-expression network analysis (WGCNA) combined with machine learning and further validated by the Human Protein Atlas (HPA) database. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the biomarker panel.

Results: There was a clear distinction in proteomic features among CGC, CHGD, CLGD, and the healthy controls. According to the WGCNA, we found 42 positively associated and 164 inversely associated proteins related to CGC progression and demonstrated several canonical cancer-associated pathways. Combined with the results from random forests, LASSO regression, and immunohistochemical results from the HPA database, we identified three candidate proteins (GSTP1, CSRP1, and LY6G6F) that could together distinguish CLGD (AUC = 0.91), CHGD (AUC = 0.99) and CGC (AUC = 0.98) from healthy controls with excellent accuracy.

Conclusions: The panel of protein biomarkers showed promising diagnostic potential for CGC and precancerous lesions. Further validation and a larger-scale study are warranted to assess its potential clinical applications, suggesting a potential avenue for CGC prevention in the future.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256680PMC
http://dx.doi.org/10.1016/j.jncc.2023.10.003DOI Listing

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