靶向血浆蛋白质组学分析揭示了用于早期诊断胃癌的高性能生物标志物组合。

Targeted plasma proteomic analysis uncovers a high-performance biomarker panel for early diagnosis of gastric cancer.

机构信息

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.

Laboratory for Aging and Cancer Research, Frontiers Science Center Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

出版信息

Clin Chim Acta. 2024 May 15;558:119675. doi: 10.1016/j.cca.2024.119675. Epub 2024 Apr 15.

DOI:10.1016/j.cca.2024.119675

PMID:38631604

Abstract

BACKGROUND

Gastric cancer (GC) is characterized by high morbidity, high mortality and low early diagnosis rate. Early diagnosis plays a crucial role in radically treating GC. The aim of this study was to identify plasma biomarkers for GC and early GC diagnosis.

METHODS

We quantified 369 protein levels with plasma samples from discovery cohort (n = 88) and validation cohort (n = 50) via high-throughput proximity extension assay (PEA) utilizing the Olink-Explore-384-Cardiometabolic panel. The multi-protein signatures were derived from LASSO and Ridge regression models.

RESULTS

In the discovery cohort, 13 proteins (GDF15, ITIH3, BOC, DPP7, EGFR, AMY2A, CCDC80, CD163, GPNMB, LTBP2, CTSZ, CCL18 and NECTIN2) were identified to distinguish GC (Stage I-IV) and early GC (HGIN-I) groups from control group with AUC of 0.994 and AUC of 0.998, severally. The validation cohort yielded AUC of 0.930 and AUC of 0.818 for GC and early GC, respectively.

CONCLUSIONS

This study identified a multi-protein signature with the potential to benefit clinical GC diagnosis, especially for Asian and early GC patients, which may contribute to the development of a less-invasive, convenient, and efficient early screening tool, promoting early diagnosis and treatment of GC and ultimately improving patient survival.

摘要

背景

胃癌（GC）的发病率、死亡率均较高，早期诊断率较低。早期诊断对根治性治疗 GC 至关重要。本研究旨在寻找 GC 和早期 GC 的血浆生物标志物。

方法

我们利用 Olink-Explore-384-Cardiometabolic 面板，通过高通量邻近延伸分析（PEA）对来自发现队列（n=88）和验证队列（n=50）的血浆样本进行了 369 种蛋白质水平的定量分析。多蛋白标志物是通过 LASSO 和 Ridge 回归模型得到的。

结果

在发现队列中，有 13 种蛋白质（GDF15、ITIH3、BOC、DPP7、EGFR、AMY2A、CCDC80、CD163、GPNMB、LTBP2、CTSZ、CCL18 和 NECTIN2）被鉴定为能够区分 GC（I-IV 期）和早期 GC（HGIN-I）与对照组，AUC 分别为 0.994 和 0.998。验证队列的 GC 和早期 GC 的 AUC 分别为 0.930 和 0.818。