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Alpha-fetoprotein (AFP) accounted for 1/3 of the total plasma protein in the fetus at 13 weeks, reached the highest peak at 30 weeks of gestation, and then gradually decreased. The plasma concentration at birth was about 1% of the peak period: about 40 mg / L, close to the adult level (less than 20 μg / L) at the age of one year. When hepatocytes regenerate after cancer or injury, the function of producing AFP is restored. As the condition worsens, the level of AFP in serum will rise sharply. In addition, there are different degrees of elevation of AFP in pregnancy, some gastrointestinal tumors, acute and chronic liver diseases. With the deepening of its research, the application value of AFP in various diseases is gradually reflected.
Tahtouh et al. showed that the inhibition of telomerase, PKC and PI3K/Akt/mTOR/STAT3 signaling pathways resulted in decreased AFP expression and secretion. In contrast, inhibition of the MAPK/ERK pathway did not show any effect. Telomerase regulation of AFP may be through the PI3K/Akt/mTOR/STAT3 signaling pathway or through an independent pathway. Further research is needed to elucidate the regulation of telomerase on AFP.
Figure 1. Schematic representation of intracellular signaling pathways leading to AFP expression and secretion. (Tahtouh, et al. 2015)
Diagnostic Value of AFP
AFP is currently the most commonly used method for diagnosing liver cancer and the most important tumor index. The diagnostic criteria are AFP ≥ 400 μg/L. This can exclude chronic or active hepatitis, cirrhosis, testicular or ovarian embryogenic tumors, and pregnancy. About 60% to 70% of patients with liver cancer have elevated AFP, of which about 18% of patients with liver cancer have low AFP levels, and about 30% of patients with liver cancer have normal AFP levels.
Hepatitis B virus (HBV) and/or Hepatitis C virus (HCV) infection, long-term alcohol abuse, non-alcoholic steatohepatitis, food contaminated with aflatoxin, and the men have the family history of liver cirrhosis and liver cancer, especially in men over 40 years old, is defined as a high-risk group of liver cancer. It is recommended to conduct a screening test at least every 6 months with B-ultrasound. AFP plays an important role in evaluating the efficacy of various treatments for liver cancer. The criteria for the radical resection of liver cancer require no tumor lesions were found. If the preoperative AFP is elevated, AFP is required 2 months’ quantitative determination after surgery until the level of AFP is in the normal range (very few patients have AFP down to normal for more than 2 months). After liver transplantation, TACE, radiofrequency ablation of liver cancer, targeted therapy, and radiotherapy and chemotherapy, continuous increase in serum AFP levels often suggests a poor prognosis.
Combined Detection of AFP, AFP⁃L3, and Abnormal Prothrombin (DCP)
AFP ⁃L is a glycoprotein which can be divided into three types according to its affinity with lentil lectin (LCA) on affinity electrophoresis, namely AFP⁃L1, AFP⁃L2 and AFP⁃L3. AFP⁃L3 is mainly derived from liver cancer cells, which makes it closely related to liver cancer. Related studies have shown that high levels of AFP⁃L3 before treatment indicate a poor prognosis for primary liver cancer (PHC). In recent years, AFP⁃L3 has been used as an important marker to detect PHC and is widely used in clinical practice.
LIM et al. selected 361 patients with hepatocellular carcinoma as the study object, and analyzed the data by detecting the levels of AFP, AFP⁃L3 and DCP in the serum to diagnose PHC. When AFP, AFP⁃L3, and DCP are combined, the diagnostic accuracy is significantly better than their separate detection. CHOI et al. selected 90 patients with hepatocellular carcinoma and found that the combined detection of AFP⁃ L3 and DCP is up to 90% sensitive for those with early, single, small, and low-concentration AFP. This is important for clinically improving the accuracy of PHC diagnosis.
BEST et al. selected 285 patients with hepatocellular carcinoma and found that the combined detection of AFP, AFP, L3, and DCP has the highest sensitivity compared with the single test, suggesting the significance for early AFP-negative hepatocellular carcinoma.
Joint Detection of AFP, DCP, DKK1
DKK1 is a secreted inhibitory factor and is closely related to Wnt signaling pathway. FOUAD et al. found that DKK1 may be a key regulator of hepatocellular carcinoma progression and a potential target for the treatment of liver cancer. ERDAL and other studies have found that the combined detection of DKK1 and AFP for the diagnosis of hepatocellular carcinoma is superior to the separate detection.
Eighty-six patients with liver cancer were selected as their own subjects, and their AFP, DCP, and DKK1 levels were measured. The data were analyzed to obtain AFP, DCP, and DKK1 with sensitivity of 58.13%, 74.42%, and specificity of 73.26%. 29.00%, 30.00%, and 44.00%, the sensitivity and specificity of the combined detection were 93.02% and 78.00%, respectively. This study demonstrates that AFP, DCP, and DKK1 combined with hepatocellular carcinoma have higher sensitivity and specificity than those of the single test, which is important for clinical diagnosis of hepatocellular carcinoma.