Serological Biomarkers for Early Detection of Hepatocellular Carcinoma: A Focus on Autoantibodies against Tumor-Associated Antigens Encoded by Cancer Driver Genes.

Keyan Wang,Miao Li,Jianying Zhang,Jianxiang Shi,Liping Dai,Lin Cheng,Xiao Wang,Di Jiang,Qian Yang,Peng Wang,Hua Ye,Cuipeng Qiu,Guiying Sun,Jiejie Qin

doi:10.3390/cancers12051271

Abstract

Substantial evidence manifests the occurrence of autoantibodies to tumor-associated antigens (TAAs) in the early stage of hepatocellular carcinoma (HCC), and previous studies have mainly focused on known TAAs. In the present study, protein microarrays based on cancer driver genes were customized to screen TAAs. Subsequently, autoantibodies against selected TAAs in sera were tested by enzyme-linked immunosorbent assays (ELISA) in 1175 subjects of three independent datasets (verification dataset, training dataset, and validation dataset). The verification dataset was used to verify the results from the microarrays. A logistic regression model was constructed within the training dataset; seven TAAs were included in the model and yielded an area under the receiver operating characteristic curve (AUC) of 0.831. The validation dataset further evaluated the model, exhibiting an AUC of 0.789. Remarkably, as the aggravation of HCC increased, the prediction probability (PP) of the model tended to decrease, the trend of which was contrary to alpha-fetoprotein (AFP). For AFP-negative HCC patients, the positive rate of this model reached 67.3% in the training dataset and 50.9% in the validation dataset. Screening TAAs with protein microarrays based on cancer driver genes is the latest, fast, and effective method for finding indicators of HCC. The identified anti-TAA autoantibodies can be potential biomarkers in the early detection of HCC.

Highlights

IntroductionIt was estimated that only approximately 10% of hepatocellular carcinoma (HCC) patients can be detected in the early stage and is suitable for surgical resection [3,4]
Hepatocellular carcinoma is the third leading cause of cancer death worldwide [1,2]
In the subsequent validation phase, all serum samples, including 127 liver cirrhosis (LC) sera and 449 hepatocellular carcinoma (HCC) sera as well as 449 normal controls (NCs) sera matched to HCC patients by age and gender, were obtained from the same serum bank of Tumor Epidemiology Laboratory of Zhengzhou

Summary

Introduction

It was estimated that only approximately 10% of HCC patients can be detected in the early stage and is suitable for surgical resection [3,4]. This phenomenon is mainly attributed to the absence of effective early diagnostic markers [5,6,7]. Compared with other serological diagnostic biomarkers of HCC, such as circulating cell-free DNA [11], TAAs themselves [12], cytokines [13], or RNA [14], autoantibodies enlarged by the immune system are more stable and durable, are more measured, and require less blood to be drawn from the patients, making them ideal noninvasive biomarkers [15,16,17,18,19,20,21,22]. It is necessary to identify novel representative TAAs for the detection of HCC

Methods

Results

Discussion

Conclusion