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

蛋白质组学 生物标志物 发育不良 癌症 接收机工作特性 图谱 Lasso(编程语言) 肿瘤科 医学 内科学 生物信息学 生物 计算生物学 病理 基因 蛋白质表达 遗传学 计算机科学 万维网
作者
Jianhua Gu,Shuanghua Xie,Xinqing Li,Zeming Wu,Liyan Xue,Shaoming Wang,Wenqiang Wei
出处
期刊:Journal of the National Cancer Center [Elsevier]
卷期号:3 (4): 286-294 被引量:1
标识
DOI:10.1016/j.jncc.2023.10.003
摘要

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. 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 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. 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. 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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