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Figure S6 from High-Throughput Peptide Arrays Identify Potential Diagnostic Autoantibody Signatures in Early-Stage Lung Adenocarcinoma

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posted on 2023-05-01, 08:40 authored by Rongrong Luo, Pei Zhong, Xiying Li, Juan Cai, Yimin Tao, Bangzhu Xiong, Hancheng Zheng, Zhishang Zhang, Le Tang, Jiarui Yao, Yingrui Li, Yuankai Shi, Xiaohong Han

Random forest model and GO enrichment. a, Schematic plot of random forest; b, GO terms enriched by the matched proteins of differential peptide probes.

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National Natural Science Foundation of China (NSFC)

Chinese Academy of Medical Sciences (CAMS)

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ARTICLE ABSTRACT

Early diagnosis is critical to lung adenocarcinoma patients’ survival but faces inadequacies in convenient early detection. We applied a comprehensive microarray of 130,000 peptides to detect “autoantibody signature” that is autoantibodies binding to mimotopes for early detection of stage 0–I LUAD. Plasma samples were collected from 147 early-stage lung adenocarcinoma (Early-LUAD), 108 benign lung disease (BLD), and 122 normal healthy controls (NHC). Clinical characteristics, low-dose CT (LDCT), and laboratory tests were incorporated into correlation analysis. We identified 143 and 133 autoantibody signatures, distinguishing Early-LUAD from NHC/BLD in the discovery cohort. Autoantibody signatures significantly correlated with age, stage, tumor size, basophil count, and IgM level (P < 0.05). The random forest models based on differential autoantibody signatures displayed AUC of 0.92 and 0.87 to discern Early-LUAD from NHC/BLD in the validation cohort, respectively. Compared with LDCT, combining autoantibody signature and LDCT improved the positive predictive value from 50% to 78.33% (P = 0.049). In addition, autoantibody signatures displayed higher sensitivity of 72.4% to 81.0% compared with the combinational tumor markers (cyfra21.1, NSE, SCC, ProGRP) with a sensitivity of 22.4% (P = 0.000). Proteins matched by differential peptides were enriched in cancer-related PI3K/Akt, MAPK, and Wnt pathways. Overlaps between matched epitopes and autoantibody signatures illustrated the underlying engagement of autoantibodies in immune recognition. Collectively, autoantibody signatures identified by a high-throughput peptide microarray have the potential to detect Early-LUAD, which could assist LDCT to better diagnose Early-LUAD. Novel sensitive autoantibody signatures can adjuvant LDCT to better diagnose LUAD at very early stage.

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    Cancer Epidemiology, Biomarkers & Prevention

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