Advances in tumour markers for diagnosis of hepatocellular carcinoma

Abstract

According to the data from the Chinese Centre for Disease Control and Prevention, the liver cancer ranks second among malignant tumour deaths in China, with a high mortality rate. Liver cancer is characterized by difficult of early diagnosis (about 50% of patients missed), high malignant level, strong heterogeneity, and rapid progression. Early diagnosis can help patients seize the best chance for treatment, reduce the damage to the body, improve the treatment effect, and prolong survival. The main pathological type of liver cancer is hepatocellular carcinoma(HCC). Commonly used clinical tumour markers for HCC include α-fetoprotein (AFP), protein induced by vitamin K deficiency or antagonist-Ⅱ (PIVKA-Ⅱ), a-L-fucosidase (AFU), etc., which are simple and efficient. However, due to the heterogeneity of liver cancer, the marker levels in some patients were not abnormal, and 52% of HCC patients with small tumours (<3 cm) were AFP-negative, which affected the diagnostic accuracy of HCC. Therefore, some novel tumour markers have been discovered, including circulating tumour cells (CTCs), circulating cell-free nucleic acids [including circulating cell-free DNA (cfDNA) and microRNAs (miRNAs)], and exosomes. It revealed that 90.81% of CTC positive HCC patients (including early disease patients) can detect very small HCC nodules after 3-5 months of follow-up, indicating a high correlation between CTC and HCC characteristics. Postoperative monitoring of CTC levels can predict HCC recurrence before clinical detection of recurrent nodules; cfDNA can serve as an effective tool for early diagnosis of HCC, and detecting mutations in ctDNA can guide targeted therapy; miRNA can serve as a biomarker for diagnosing diseases and monitoring disease progression and prognosis; The joint detection of AFP and lncRNAs panel (including three circulating exosome sources of long chain non coding RNAs: ENSG00000248932.1, ENST000000440688.1, ENST000000457302.2) showed higher sensitivity and specificity than the single detection of AFP (AUC: 0.910 and 0.408), which can predict the occurrence of HCC and dynamically monitor HCC metastasis.However, these new tumour markers still have some limitations such as high false-negative rate at low levels, and limitation in stability due to the lack of standardized pre-analytical variables and analytical variables. These tumour markers are still not recommended to be used independently for early screening, monitoring or large-scale clinical application of HCC, and can only be used as a supplement to traditional diagnostic methods. This article reviewed the research progress of tumour markers in the diagnosis of HCC in recent years, summarized the efficacy of traditional tumour markers (AFP, PIVKA-Ⅱ. and AFU, etc.), introduced the research progress and clinical application of new tumour markers (CTC, cfDNA, ctDNA, miRNA and exosomes, etc.), and looked forward to improving the accuracy of HCC diagnosis in the future.

Keywords

• |tumour marker|liver cancer|tumour diagnosis|detection method