Hepatocellular carcinoma diagnosis using a novel electrochemiluminescence immunoassay targeting serum IgM-free AIM

• DOI: 10.1007/s12328-021-01567-4
• Publication Date: 2022-01-04T00:03:41Z
• Authors: Tomo Shimizu; Takashi Sawada; Tomohide Asai; Yuka Kanetsuki; Jiro Hirota; Michihisa Moriguchi; Tomoaki Nakajima; Toru Miyazaki; Takeshi Okanoue
• Keywords: Immunoassay; Receptors, Scavenger; Carcinoma, Hepatocellular; Non-alcoholic Fatty Liver Disease; Macrophages; Liver Neoplasms; Biomarkers, Tumor; Humans; Original Article; Prothrombin; alpha-Fetoproteins; Apoptosis Regulatory Proteins; 3. Good health

AbstractBackgroundRecent increases in the number of patients with non-alcoholic steatohepatitis (NASH) warrant the identification of biomarkers for early detection of hepatocellular carcinoma (HCC) associated with NASH (NASH-HCC). IgM-free apoptosis inhibitor of macrophage (AIM), which generally associates with IgM in blood and exerts its biological function by dissociation from IgM, may serve as an effective biomarker for NASH-HCC. Here, we established a fully automatic and high-throughput electrochemiluminescence immunoassay (ECLIA) to measure IgM-free AIM and investigated its efficacy in diagnosing NASH-HCC and viral HCC.MethodsIgM-free AIM levels were measured in 212 serum samples from patients with, or without, HCC related to NASH, hepatitis B virus, and hepatitis C virus, using ECLIA. We also developed an ECLIA for measuring both IgM-free and IgM-bound AIM and investigated the existing form of AIM in blood by size-exclusion chromatography.ResultsIgM-free AIM levels were significantly higher in the HCC group than in the non-HCC group, regardless of the associated pathogenesis. Moreover, the area under the receiver operating curve for IgM-free AIM was greater than that for conventional HCC biomarkers, alpha-fetoprotein or des-γ-carboxy prothrombin, regardless of the cancer stage. ECLIA counts of IgM-free AIM derived from samples fractionated by size-exclusion chromatography were significantly higher in patients with NASH-HCC than in healthy volunteers and in patients with non-alcoholic fatty liver and NASH.ConclusionsSerum IgM-free AIM may represent a universal HCC diagnostic marker superior to alpha-fetoprotein or des-γ-carboxy prothrombin. Our newly established ECLIA could contribute to further clinical studies on AIM and in vitro HCC diagnosis.