Proteomics-driven noninvasive screening of circulating serum protein panels for the early diagnosis of hepatocellular carcinoma

Xiaohua Xing, Linsheng Cai, Jiahe Ouyang, Fei Wang, Zongman Li, Mingxin Liu, Yingchao Wang, Yang Zhou, En Hu, Changli Huang, Liming Wu (), Jingfeng Liu () and Xiaolong Liu ()
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Xiaohua Xing: Mengchao Hepatobiliary Hospital of Fujian Medical University
Linsheng Cai: Mengchao Hepatobiliary Hospital of Fujian Medical University
Jiahe Ouyang: Mengchao Hepatobiliary Hospital of Fujian Medical University
Fei Wang: Mengchao Hepatobiliary Hospital of Fujian Medical University
Zongman Li: Mengchao Hepatobiliary Hospital of Fujian Medical University
Mingxin Liu: Mengchao Hepatobiliary Hospital of Fujian Medical University
Yingchao Wang: Mengchao Hepatobiliary Hospital of Fujian Medical University
Yang Zhou: Mengchao Hepatobiliary Hospital of Fujian Medical University
En Hu: Mengchao Hepatobiliary Hospital of Fujian Medical University
Changli Huang: Clinical Oncology School of Fujian Medical University
Liming Wu: Mengchao Hepatobiliary Hospital of Fujian Medical University
Jingfeng Liu: Clinical Oncology School of Fujian Medical University
Xiaolong Liu: Mengchao Hepatobiliary Hospital of Fujian Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Early diagnosis of hepatocellular carcinoma (HCC) lacks highly sensitive and specific protein biomarkers. Here, we describe a staged mass spectrometry (MS)-based discovery-verification-validation proteomics workflow to explore serum proteomic biomarkers for HCC early diagnosis in 1002 individuals. Machine learning model determined as P4 panel (HABP2, CD163, AFP and PIVKA-II) clearly distinguish HCC from liver cirrhosis (LC, AUC 0.979, sensitivity 0.925, specificity 0.915) and healthy individuals (HC, AUC 0.992, sensitivity 0.975, specificity 1.000) in an independent validation cohort, outperforming existing clinical prediction strategies. Furthermore, the P4 panel can accurately predict LC to HCC conversion (AUC 0.890, sensitivity 0.909, specificity 0.877) with predicting HCC at a median of 11.4 months prior to imaging in prospective external validation cohorts (No.: Keshen 2018_005_02 and NCT03588442). These results suggest that proteomics-driven serum biomarker discovery provides a valuable reference for the liquid biopsy, and has great potential to improve early diagnosis of HCC.

Date: 2023
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DOI: 10.1038/s41467-023-44255-2

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