Serum fetoprotein
Serum alpha fetoprotein (alpha fetoprotein, AFP) is an important indicator for the diagnosis of hepatocellular carcinoma and the most specific tumor marker, and is commonly used in China for screening, early diagnosis, postoperative surveillance, and follow-up of hepatocellular carcinoma.
The sensitivity of AFP for hepatocellular carcinoma is 39% to 65% and the specificity is 76% to 94%, yet about 40% of patients with hepatocellular carcinoma have normal AFP levels. By detecting AFP heterodimers, it can help improve the diagnosis of early hepatocellular carcinoma.
For AFP not less than 400 ug/L for more than 1 month or not less than 200 ug/L for 2 months, there should be a high suspicion of hepatocellular carcinoma after excluding pregnancy, germinal germ tumors, and active liver disease.
AFP is divided into three different isoforms, AFP-L1, AFP-L2, and AFP-L3. AFP-L3 is expressed only in patients with hepatocellular carcinoma (HCC), and AFP-L3-positive hepatocellular carcinoma is characterized by rapid growth and early metastasis.
In patients with small hepatocellular carcinoma (hepatocellular carcinoma with a tumor diameter of less than 3 cm), the sensitivity and specificity of AFP-L3 for early diagnosis are 75%-96.90% and 90%-92%, respectively, and can be used as one of the indicators for early diagnosis of hepatocellular carcinoma.
Abnormal prothrombin
Abnormal prothrombin, also known as des-gamma-carboxyprothrombin (DCP), is an abnormal prothrombin caused by incomplete carboxylation of precursors during prothrombin synthesis in the liver, and DCP levels are significantly elevated in patients with hepatocellular carcinoma.
DCP has high sensitivity and specificity in the screening and diagnosis of hepatocellular carcinoma, 51.7% and 86.7%, respectively. dCP is significantly better than AFP and is a tumor marker for early diagnosis and monitoring of recurrence and metastasis of hepatocellular carcinoma.
In addition to liver cancer screening, serum DCP can be used as a clinicopathological or prognostic indicator for patients with hepatocellular carcinoma and may be a better indicator of the aggressiveness of liver cancer than AFP.
α-L-amyloidase
α-L-fucosidase (AFU), a lysosomal acid hydrolase, is widely distributed in human cells and body fluids, with the highest content in liver and kidney tissues, and is mainly responsible for hydrolyzing the fucosyl bonds of glycoproteins and glycolipids.
AFU can be used as a new marker for the diagnosis of primary liver cancer with good sensitivity and specificity. Persistently elevated serum AFU levels in patients with cirrhosis contribute to the early detection of primary liver cancer. In 70% to 85% of AFP-negative hepatocellular carcinoma cases, AFU is positive, and the rate of serum AFU positivity is higher in patients with small hepatocellular carcinoma than in AFP.
Serum AFU is elevated early in the development of hepatocellular carcinoma, independent of the size of the tumor, and is relied on for the early diagnosis of hepatocellular carcinoma at least 6 months earlier than by ultrasound. The AFU can assist in the early diagnosis of hepatocellular carcinoma, as it can increase the positive detection rate from 70% to 90% when combined with AFP.
Golgi glycoprotein 73
Golgi protein 73 (GP73) is a 73kD Golgi membrane protein. GP73 expression is upregulated in hepatocytes from patients with acute hepatitis, cirrhosis, and hepatocellular carcinoma, and is significantly elevated in the serum of patients who develop hepatocellular carcinoma.
The sensitivity and specificity of GP73 in the diagnosis of hepatocellular carcinoma are 69% and 75%, respectively, which is significantly higher than that of AFP, and can be used as a marker for early screening and diagnosis of hepatocellular carcinoma. In about 50% of patients with low AFP expression, GP73 expression is significantly elevated, so GP73 can improve the early diagnosis of patients with low AFP expression. Therefore, the combined detection of AFP and GP73 can improve the diagnosis of early hepatocellular carcinoma.
Phosphatidylinositol proteoglycan 3
Phosphatidylinositol proteoglycan 3 (GPC 3) is a member of the phosphatidylinositol proteoglycan family, which is involved in regulating cell proliferation and survival during embryonic development and acts as a tumor suppressor. abnormal expression of GPC 3 is closely associated with the development and progression of many tumors.
GPC 3 was first identified as a potential diagnostic marker for hepatocellular carcinoma in 1997. gPC 3 is barely expressed in hepatocytes from healthy individuals and patients with non-malignant liver disease, whereas it is highly expressed in the serum of 50% of patients with hepatocellular carcinoma, and is elevated in approximately 33% of patients with AFP- and DCP-negative hepatocellular carcinoma.
In patients with low AFP expression, co-testing for GPC 3 may improve the diagnostic sensitivity. GPC 3 is still expressed in small early lesions of hepatocellular carcinoma, but not in cirrhosis or regenerative nodules, so GPC 3 can be used as an early diagnostic marker for hepatocellular carcinoma.
Bone bridging protein
Osteopontin (OPN) is a highly phosphorylated and glycosylated calcium-binding secretory protein that is widely expressed in cells in vivo and has functions in cell adhesion and migration, immune and inflammatory responses, anti-apoptosis, inhibition of nitric oxide synthase, and osteocalcin.
The OPN has been found to be essential in the spread of various cancers and its elevated expression is associated with tumor invasion, progression, metastasis.
Serum levels of OPN are significantly elevated in patients with hepatocellular carcinoma, with a diagnostic sensitivity of 75%, significantly higher than AFP. In patients with hepatitis B-positive hepatocellular carcinoma, elevated tumor tissue OPN is associated with portal vein and lymph node infiltration and worse prognosis, suggesting the use of OPN as a marker for early diagnosis and treatment prognosis of hepatocellular carcinoma.
Glutamyltransferase
Glutamyl transferase (γ-glutamyl transpeptadase, GGT) is found primarily in kidney, liver, and pancreas, with the kidney being the most abundant, followed by the liver and pancreas. In the liver, it is mainly found in hepatocytes and bile duct epithelial cells, and GGT in normal human serum is mainly from the liver.
GGT can be significantly elevated in patients with hepatocellular carcinoma, and is particularly useful in the differential diagnosis of patients with small hepatocellular carcinoma or AFP-negative hepatocellular carcinoma. However, it is less specific, and GGT activity can be elevated in liver, biliary, and pancreatic disease.