UNASSIGNED: This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level.
UNASSIGNED: In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation.
UNASSIGNED: The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC.
■这项研究分三个阶段进行(发现阶段,验证阶段,和评估阶段),共包括744名参与者。首先,使用蛋白质微阵列发现了抗BIRC5自身抗体,与正常对照样品(NC)相比,ANHCC样品(ANHCC)的阳性率更高。其次,通过酶联免疫吸附试验(ELISA),在来自两个临床中心(郑州和南昌)的85例ANHCCs和85例NCs中验证了抗BIRC5自身抗体.最后,在由另外149个AFP阳性肝细胞癌样本(APHCC)组成的队列中,通过ELISA评估了抗BIRC5自身抗体对肝细胞癌(HCC)的诊断有效性,95个ANHCCs和244个NC。升高的自身抗体与肝癌中BIRC5的高表达的关联由来自预后的数据库进一步探索,免疫浸润,DNA甲基化,和基因突变水平。
■在验证阶段,郑州和南昌中心抗BIRC5自身抗体区分ANHCC和NCs的ROC曲线下面积(AUC)分别为0.733和0.745。在评估阶段,用于鉴定ANHCC和来自NC的HCC的抗BIRC5自身抗体的AUC分别为0.738和0.726。此外,当与AFP结合时,鉴定来自NC的HCC的AUC增加到0.914,敏感性为77.5%,特异性为91.8%.BIRC5基因的高表达不仅与HCCs的不良预后相关,但也与免疫细胞的浸润密切相关,DNA甲基化,和基因突变。
■研究结果表明,抗BIRC5自身抗体可以作为ANHCC的潜在生物标志物,除了AFP在HCC诊断中的辅助作用。接下来,我们可以进行具体验证,探讨抗BIRC5自身抗体在HCC发生发展中的作用。