Abstract
More efficient biomarkers are needed to facilitate the early detection of hepatocellular carcinoma (HCC). We aimed to identify candidate biomarkers for HCC detection by proteomic analysis. First, we performed a global proteomic analysis of 10 paired HCC and non-tumor tissues. Then, we validated the top-ranked proteins by targeted proteomic analyses in another tissue cohort. At last, we used enzyme-linked immunosorbent assays to validate the candidate biomarkers in multiple serum cohorts including HCC cases (HCCs), cirrhosis cases (LCs), and normal controls (NCs). We identified and validated 33 up-regulated proteins in HCC tissues. Among them, eight secretory or membrane proteins were further evaluated in serum, revealing that aldo–keto reductase family 1 member B10 (AKR1B10) and cathepsin A (CTSA) can distinguish HCCs from LCs and NCs. The area under the curves (AUCs) were 0.891 and 0.894 for AKR1B10 and CTSA, respectively, greater than that of alpha-fetoprotein (AFP; 0.831). Notably, combining the three proteins reached an AUC of 0.969, which outperformed AFP alone (P < 0.05). Furthermore, the serum AKR1B10 levels dramatically decreased after surgery. AKR1B10 and CTSA are potential serum biomarkers for HCC detection. The combination of AKR1B10, CTSA, and AFP may improve the HCC diagnostic efficacy.
Highlights
More efficient biomarkers are needed to facilitate the early detection of hepatocellular carcinoma (HCC)
The recruited participants were defined as HCC cases (HCCs), liver cirrhosis cases (LCs) or healthy normal controls (NCs) by medical doctors, according to eligibility criteria listed in the Supplementary Table S1
As we aimed to identify serum biomarkers for HCC detection, the proposed potential biomarkers should have the following features: (1) it should be a secretory or membrane protein that can be released into blood; 2) it can be detected in blood reliably using a convenient and cost-effective method, such as enzyme-linked immunosorbent assays (ELISAs)
Summary
More efficient biomarkers are needed to facilitate the early detection of hepatocellular carcinoma (HCC). We aimed to identify candidate biomarkers for HCC detection by proteomic analysis. AKR1B10 and CTSA are potential serum biomarkers for HCC detection. Cui et al investigated the serum proteomic differences between patients with early recurrent spontaneous abortion and healthy controls to identify potential biomarkers by combining iTRAQ-based discovery analyses and PRM-MS-based verification analyses[22]. This integrative strategy has not been employed for identifying HCC biomarkers
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