Hao Wudi, Zhao Danyang, Meng Yuan, Yang Mei, Ma Meichen, Hu Jingwen, Liu Jianhua, Qin Xiaosong
Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China; Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China.
Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China; Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China.
Mol Cell Proteomics. 2024 Dec;23(12):100872. doi: 10.1016/j.mcpro.2024.100872. Epub 2024 Nov 1.
Hepatocellular carcinoma (HCC) is associated with one of the highest mortality rates among cancers, rendering its early diagnosis clinically invaluable. Serum biomarkers, specifically alpha-fetoprotein (AFP), represent the most promising and widely used diagnostic biomarkers for HCC. However, its detection rate is low in the early stages of HCC progression, and distinguishing specific false positives for other liver-related diseases, such as cirrhosis and acute hepatitis, remains challenging. Therefore, this study was conducted to identify biomarkers for hepatitis B (HBV)-related liver diseases by screening differentially expressed autoantibodies against tumor-associated antigens (TAAbs). We designed a large-scale multistage investigation, encompassing initial screening, HCC-focused, and ELISA validation cohorts to identify potential TAAbs in HBV-related liver diseases, spanning from healthy control (HC) individuals to patients with chronic hepatitis B (CHB), hepatitis B-related cirrhosis (HBC), and HCC, using protein microarray technology. The differential biological characteristics of TAAbs were analyzed using bioinformatics analysis. Validation of tumor-specific biomarkers for HCC was performed using ELISA. In the screening cohort, 547 candidate TAAbs were identified in the HCC group compared to those in the HC group. In the HCC-focused cohort, 64, 61, and 65 candidate TAAbs were identified in the CHB, HBC, and HCC groups, respectively, compared to those in the HC group. Thirty-four proteins exhibited continuously elevated expression from HCs to patients with CHB, HBC, and HCC. Among these, nine were identified as cancer-specific proteins. In the validation cohort, UBE2Z, CNOT3, and EID3 were correlated with liver function indicators in patients with hepatitis B-related HCC. Overall, UBE2Z, CNOT3, and EID3 emerged as cancer-specific biomarkers for HBV-related liver disease, providing a scientific basis for clinical application.
肝细胞癌（HCC）是癌症中死亡率最高的疾病之一，因此其早期诊断在临床上具有极高的价值。血清生物标志物，特别是甲胎蛋白（AFP），是HCC最具前景且应用最广泛的诊断生物标志物。然而，在HCC进展的早期阶段其检测率较低，并且区分其他肝脏相关疾病（如肝硬化和急性肝炎）的特定假阳性结果仍然具有挑战性。因此，本研究旨在通过筛选针对肿瘤相关抗原的差异表达自身抗体（TAAbs）来鉴定乙型肝炎（HBV）相关肝病的生物标志物。我们设计了一项大规模多阶段调查，包括初始筛查、聚焦HCC的队列以及ELISA验证队列，以使用蛋白质微阵列技术从健康对照（HC）个体到慢性乙型肝炎（CHB）、HBV相关肝硬化（HBC）和HCC患者中识别HBV相关肝病中的潜在TAAbs。使用生物信息学分析来分析TAAbs的差异生物学特征。使用ELISA对HCC的肿瘤特异性生物标志物进行验证。在筛查队列中，与HC组相比，HCC组中鉴定出547种候选TAAbs。在聚焦HCC的队列中，与HC组相比，CHB、HBC和HCC组中分别鉴定出64、61和65种候选TAAbs。从HC到CHB、HBC和HCC患者，有34种蛋白质的表达持续升高。其中，9种被鉴定为癌症特异性蛋白质。在验证队列中，UBE2Z、CNOT3和EID3与HBV相关HCC患者的肝功能指标相关。总体而言，UBE2Z、CNOT3和EID3成为HBV相关肝病的癌症特异性生物标志物，为临床应用提供了科学依据。
