Circulating Biomarkers for Early Diagnosis of Hepatocellular Carcinoma

*Hoang Van Tong, Pham Van Dung, Nguyen Thi Mong Diep and Nguyen Linh Toan*

## **Abstract**

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, which is also often fatal. An early and accurate diagnosis is a decisive step towards the survival of the patients. Molecular biology improved significantly the prognosis of liver cancers through learned use of tumor markers like proteantigens, cytokines, enzymes, isoenzymes, circulating RNAs, gene mutations and methylations. Nevertheless, much improvement is still achievable and needed in this area, which is crucial in order to make an early diagnosis and monitor the progression of the disease. We present in this review what we believe to be the most relevant data regarding tissue and serum biomarkers related to HCC.

**Keywords:** Biomarkers, Hepatocellular Carcinoma, Diagnosis, Liver Cancer

#### **1. Introduction**

Hepatocellular carcinoma (HCC) is the fifth most common cancer in males, the seventh in females, and the third leading cause of cancer-related deaths. Each year there are approximately 800,000 fatalities [1–3]. In developing countries, morbidity and mortality rates are 84% and 83%, respectively [4]. HCC typically occurs in the context of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, accounting for 85% of all HCC cases globally [3]. Lower risk factors include nonalcoholic fatty liver disease (NAFLD) and chronic alcohol consumption [4].

Tumor evolution is a complex process implying many stages and involving many factors, such as genetic and chromosomal changes. During tumor development, the number, type, extent, and distribution of markers and variants are closely related to the occurrence, progression, invasion, and metastasis of HCC. Therefore, diagnosis and early detection are highly important in management and treatment because it is only possible to cure the disease when the tumor when it is detected at a small size.

Advances in the understanding of tumor biology, combined with the development of molecular methods in looking for new biomarkers in the early detection of the disease, their invasiveness, likelihood of metastasis and recurrence, has led to the discovery and use of several new markers in this disease. In this review, we discuss the results of the studies that we consider the most relevant, and in particular their diagnostic performance for the detection of HCC at an early stage.
