Serum biomarkers and ultrasensitive biosensors for diagnosis of early-stage hepatocellular carcinoma

Hepatocellular carcinoma (HCC) was the third leading cause of cancer-related death globally in 2020. The treatment of the disease is complex, with a high possibility of disease recurrence. The low survival rate of HCC patients is due to their late-stage diagnosis. Hence, the best prognosis is to diagnose HCC at an early stage. The diagnosis of HCC is made through imaging methods and, in selected cases, by biopsy. These diagnostic tools fail for the early detection of HCC. These methods are time-consuming and expensive, especially for resource-limited healthcare settings. Therefore, the development of simple, sensitive, and rapid methods for screening is necessary for the early detection of hepatocellular carcinoma. Tremendous research efforts were made to discover new biomarkers for HCC. Gene mutations, epigenetic modifications, circulating RNA, proteins, circulating tumour cells (CTCs), and circulating tumour-derived exosomes are promising HCC biomarkers that seem to improve diagnosis significantly. On the other hand, various biosensors have provided promising technology for detecting HCC biomarkers through rapid, sensitive, cost-effective, and user-friendly applications. This review summarises the recent studies on serum HCC-based biomarkers and ultrasensitive biosensor technologies, emphasising optical, electrochemical, and mass-signal transduction.