[Seo Hyunhyo Column] Utilizing Biomarkers for Early Detection of Liver Cirrhosis and Hepatocellular Carcinoma: An Imperative Measure

[바이오타임즈] Among the tumor markers, there are some that can only be produced by specific cancer cells in the body, and cancer of a specific organ can be diagnosed immediately when an outlier is identified. This relationship is called “high organ specificity”. These classes of tumor markers include prostate and prostate cancer-associated antigen (PSA), placental, germ cell and chorionic gonadotropin (hCG), neuroendocrine and neuron-specific enolase (NSE), endocrine and various hormones, and neurotumor markers. and catecholamines (VMA), hepatocytes, germ cells and alpha-fetoprotein (AFP).

However, since most tumor markers are produced in multiple organs, it is difficult to determine where the cancer originates even if the value of a specific marker is high. For example, tumor markers such as CEA and CA19-9 are produced by cancer cells in various organs such as the stomach, colon, pancreas, and lung. Therefore, even if the marker is present in a large amount in the serum, it is not possible to determine where the cancer originates by itself.

However, since early diagnosis is important for cancer and most cancers have no specific subjective symptoms, cancer screening using tumor markers is useful, and the types of tumor markers vary greatly depending on the type of cancer. In addition, since there is no tumor marker that can detect all cancers with one test, and there are many cancers without effective tumor markers, research to find better tumor markers is ongoing.

Hepatocellular carcinoma refers to primary liver cancer that occurs in the liver. Cancer that has spread to the liver from another site is called metastatic liver cancer. Hepatocellular carcinoma accounts for more than 90% of all liver cancers, and even if this cancer is treated, 40-80% of patients will recur. It usually recurs in the liver, but can also appear in the lungs, lymph nodes, the inner wall surrounding the abdominal cavity, and the mediastinum. The ratio of male to female patients is about 4:1, and most occur after middle age. Causes include hepatitis B virus and hepatitis C virus, alcoholic liver disease, metabolic chronic liver disease, and toxic substances. In particular, 65-80% of patients with this disease in Korea are known to be hepatitis B carriers.

In the early stages, there are no symptoms, but if symptoms do appear, it is already advanced. Symptoms are mainly fatigue, abdominal pain, sometimes bloating and loss of appetite. A characteristic symptom is the feeling of a lump in the pit of the stomach, which appears in a fairly advanced state. If hepatocellular carcinoma bursts in the abdominal cavity, sudden abdominal pain and distension, low blood pressure or shock may occur.

Patients with this disease may die from progression of hepatocellular carcinoma, but there are also cases of death due to accompanying liver cirrhosis, so treatment to prevent the progression of hepatocellular carcinoma and to prevent the progression of liver cirrhosis should be implemented. If cancer is detected early and surgically performed, it can be completely cured. However, if the cancer has progressed a lot, if the liver function is poor, or if it has metastasized to other parts of the body, surgery is not possible.

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Since hepatocellular carcinoma and cirrhosis are diseases with poor prognosis, prevention and early detection are important. To do this, hepatitis B vaccine is administered, and in the case of liver tissue accompanied by non-neoplastic regenerative nodular sclerosis, it is an intermediate stage between non-neoplastic regenerating nodule and malignant hepatocellular carcinoma, which can be referred to as a pre-hepatocarcinoma lesion. It is known to contain These nodular lesions are called dysplastic nodules, and can be subdivided into low grade dysplastic nodules or high grade dysplastic nodules according to their severity.

High-grade dysplastic nodules are considered a precancerous stage of hepatocellular carcinoma, as microscopic hepatocellular carcinoma is observed in the tissue in some cases. However, even in the classification of precursor lesions of liver cancer, pathologists divide histomorphological differences into early hepatocellular carcinoma and carcinoma in situ, etc., but in the precancerous stage of liver cancer, It is debatable. Therefore, the molecular mechanism that can explain the development process of HCC from this pre-cancerous stage has not been identified.

Hepatocellular carcinoma can be histopathologically divided into four grades according to the Edmonson Grade method. It is noteworthy that the degree of differentiation and tumor size of these tumor cells reflect morphological changes well, which means that the degree of liver cancer progresses in stages, but the molecular biological mechanism for this has not yet been identified. there is.

AFP (Alpha-Fetoprotein), a representative biomarker of hepatocellular carcinoma, is a glycoprotein abnormally produced when hepatocytes are transformed and dedifferentiated into cancer cells, and is used to detect primary liver cancer, hepatitis, fetal cancer, etc., and to monitor treatment progress. It is usually made in the fetal liver or yolk sac and peaks at the 13th week. After that, the concentration rapidly decreases. An increase can mean a serious increase in tumor cells, and in general, less than 7 to 15 ng of AFP per 1 mL of blood is judged as negative. However, AFP shows low sensitivity and low specificity, especially in liver cirrhosis and early liver cancer.

Therefore, studies are being conducted on whether cirrhosis and early liver cancer can be diagnosed through several new biomarkers, and additional markers that can effectively increase the diagnosis rate of liver cirrhosis and early liver cancer are needed. It is very important to develop diagnostic reagents using new biomarkers that can track progression to liver cancer and liver cancer at an early stage with blood.

Written by Seo Hyeon-hyo (Professor, Gyeongsang National University) hhsuh@gntech.ac.kr

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