Introduction to several tumor biomarkers for diseases—part one

  • Tumors are high-risk and high-mortality diseases that pose a serious threat to human health. A large number of studies and prevention data have confirmed that early diagnosis and early treatment are the most effective ways to prevent and treat cancer and reduce mortality. Therefore, the search for cancer markers that can be used for early diagnosis has become the focus of attention. However, in addition to poor differentiation, easy metastasis and high-speed proliferation, malignant tumor cells are completely equivalent to normal cells in cytological behavior. This brings problems to tumor diagnosis and immunotherapy. Tumor markers refer to a class of substances that abnormally change due to the expression of related genes of tumor cells or collective response to tumors during tumor cell growth, proliferation, metastasis or recurrence. Tumor markers have been in existence for more than 100 years since their discovery. Since the 1960s, they have been widely used clinically and have played an important role in the discovery and treatment of tumors. With the development of biotechnology, various new markers have been discovered, and the specificity and sensitivity have been continuously improved.

    According to clinical evaluation criteria, tumor markers should have the following characteristics:

    (1) Tumor markers must be produced by malignant tumor cells and can be detected in blood, tissue fluid, secretion or tumor tissue;

    (2) Tumor markers are expressed less in normal tissues or benign tumors;

    (3) Tumor markers of a tumor can be detected in most patients with the tumor;

    (4) Tumor markers can be detected before clinical diagnosis of tumors;

    (5) The amount of tumor markers can reflect the size of the tumor;

    (6) Tumor markers can help to estimate the therapeutic effect and predict tumor recurrence and metastasis to a certain extent.

    Classification of common cancer markers:

    1. AFP Biomarker

    Alpha-Fetal Protein (AFP) is a glycoprotein belonging to the albumin family. Normally, AFP is mainly secreted by embryonic liver cells, and is also found in hepatocellular carcinoma, embryonic tumors, and some extrahepatic tumors. It can synthesize alpha-fetoprotein. AFP was discovered in fetal sera by Bergstrand and Czar in 1956, while Abelev in the former Soviet Union discovered in 1963 that AFP was mainly derived from yolk sac and placenta. Tatarinov discovered a high concentration of alpha-fetoprotein in patients with primary liver cancer in 1964. A large number of studies have shown that AFP markers are important serological markers of primary liver cancer (PHC) and are used as a PHC for diagnosis and evaluation. Sensitive indicators after administration are applied to the clinic.

    Under normal physiological conditions, alpha-fetoprotein can be used as embryonic albumin. AFP has a higher concentration in the fetal blood circulation, and it drops after birth. AFP is basically replaced by albumin from February to March after birth, and it is difficult to detect it in the blood. Fetal congenital spina bifida, neural tube defects and Down's syndrome can lead to changes in AFP content. Screening and diagnosis of the above diseases can be performed by AFP during pregnancy. In the past, AFP was considered to be a necessary protein for mammalian pregnancy. Recent studies have shown that growth states such as fetal development, liver regeneration, and tumor cell proliferation can be inhibited by AFP. It has been pointed out in the literature that AFP can escape the immunological surveillance of the Fas/FasL pathway and achieve the purpose of regulating the growth of liver cancer cells. Studies have shown that the concentration of AFP is closely related to the progress of PHC, and can be used as a monitoring index for the treatment effect and condition of PHC patients. AFP, like albumin, binds and transports fatty acids, bilirubin, steroids, Cu2+, Ni2+, and many drugs. Since the 1990s, there have been more and more researches on the use of AFP as a carrier to transport anticancer drugs such as doxorubicin, daunorubicin, cisplatin and methotrexate. AFP as a ligand carrier can be endocytosed and selectively transports the above drugs to tumor cells for therapeutic purposes.

     At present, AFP is commonly used as an important indicator for PHC diagnosis and efficacy evaluation. PHC belongs to common malignant tumors in clinic. In recent years, the incidence rate has an increasing trend, therefore, its early diagnosis and treatment are particularly important. AFP is more sensitive to early diagnosis and prognosis assessment of PHC, up to 70%, and the specificity is much higher than all other examination methods except pathology. The concentration of AFP is positively correlated with tumor size, but there are still some limitations. About 30% of PHC patients have false positives or false negatives. Because of the increase in AFP concentration in other chronic liver diseases and PHC, AFP has little significance in the differential diagnosis of liver diseases. However, some experts point out that AFP heterogeneous AFP-L3 positive PHC patients have rapid tumor growth and distant metastasis at an early stage, suggesting that AFP-L3 is a highly specific marker of PHC, so we can use AFP-L3 for PHC early diagnosis and distinguish other chronic liver diseases. At the same time, another heterogeneous AFP-L of AFP is more difficult to detect in benign liver disease, but it has higher concentration in PHC patients, so it is considered to be used for differential diagnosis of benign and malignant liver diseases. Because AFP sources are relatively special, they have a certain detection value in a variety of diseases. AFP-L3 is of great significance for monitoring the development and activity of testicular tumors. It is a sensitive index for the diagnosis and treatment evaluation of testicular non-seminoma. In recent years, the application of AFP in the diagnosis of gastric cancer has shown that AFP of gastric cancer patients. The level is significantly higher than the benign disease of the stomach. It has a high guiding significance for the early detection of gastric cancer, the choice of surgical methods and the prognosis. In addition, positive AFP or its heterogeneous bodies are also present in pediatric diseases such as gonad and extragonadal yolk sac tumors.

    To be continued in Part One.