Introduction to common tumor markers

AFP is a glycoprotein synthesized by the liver and yolk sac during embryonic stage, and its content in the blood circulation of normal adults is minimal <20μg/L. AFP is the best marker for the diagnosis of primary liver cancer, with a positive diagnostic rate of 60%-70%. If serum AFP >400μg/L for 4 weeks or 200-400μg/L for 8 weeks, combined with imaging examination, the diagnosis of primary liver cancer can be made. In patients with acute and chronic hepatitis and cirrhosis, the concentration of AFP in serum may be increased to different degrees, but the level is often less than 300ug/L. Germinal tumors (testicular cancer, teratoma) may have increased AFP content. 2.Cancer embryonic antigen (CEA) is a glycoprotein embryonic antigen found in fetal and colon cancer tissues, which is a broad-spectrum tumor marker. The normal reference value of serum CEA is <5μg/L. The positive rate of CEA in malignant tumors is colon cancer (70%), gastric cancer (60%), pancreatic cancer (55%), lung cancer (50%), breast cancer (40%), ovarian cancer (30%), uterine cancer (30%) in order. CEA is an adhesion molecule, which is an important marker of metastasis and recurrence of many tumors. The sensitivity of CA125 for ovarian epithelial cancer can reach about 70%. Other non-ovarian malignancies (cervical cancer, uterine body cancer, endometrial cancer, pancreatic cancer, lung cancer, gastric cancer, colon/rectal cancer, breast cancer) also have a certain positive rate. Benign gynecological diseases (pelvic inflammatory disease, ovarian cysts, etc.) and early pregnancy may show varying degrees of elevated serum CA125 levels. 4.Cancer antigen 15-3 (CA15-3) CA15-3 can be used as an adjuvant diagnosis of breast cancer, postoperative follow-up and indicator of metastatic recurrence. It has low sensitivity (60%) for early stage breast cancer, 80% for late stage, and high positive rate (80%) for metastatic breast cancer. Other malignant tumors also have a certain positive rate, such as: lung cancer, colon cancer, pancreatic cancer, ovarian cancer, cervical cancer, primary liver cancer, etc. 5.Glycan antigen 19-9 (CA19-9) CA19-9 is a glycan antigen associated with gastrointestinal cancer, usually distributed in normal fetal pancreas, gallbladder, liver, intestine and normal adult pancreatic and bile duct epithelium. Testing patients' serum CA19-9 can be used as an auxiliary diagnostic indicator for pancreatic cancer, gallbladder cancer and other malignant tumors, and is of great significance in monitoring changes in disease and recurrence. Serum CA19-9 levels are also elevated to varying degrees in patients with gastric cancer, colon/rectal cancer, liver cancer, breast cancer, ovarian cancer, lung cancer, etc. Certain inflammatory diseases of the gastrointestinal tract also have different degrees of elevated CA19-9, such as: acute pancreatitis, cholecystitis, cholestatic cholangitis, hepatitis, cirrhosis, etc. CA50 is a marker of pancreatic and colorectal cancer and is the most commonly used glycoantigen tumor marker, because it is widely present in the pancreas, gallbladder, liver, stomach, colorectum, bladder and uterus, and its tumor recognition spectrum is wider than CA19-9, so it is also a universal tumor marker-related antigen, rather than a tumor marker specific to an organ. CA50 can be detected in various malignant tumors with different positive rates. The positive detection rate of pancreatic cancer and gallbladder cancer is the first one, accounting for 94.4%; the others are liver cancer (88%), ovarian and uterine cancer (88%) and malignant pleural fluid (80%). It can be used for the early diagnosis of pancreatic cancer, gallbladder cancer and other tumors, and also has high value for the diagnosis of liver cancer, stomach cancer, colorectal cancer and ovarian cancer. CA242 is a glycolipid antigen related to pancreatic cancer, gastric cancer and colorectal cancer. Serum CA242 has good sensitivity (80%) and specificity (90%) for the adjuvant diagnosis of pancreatic cancer and colorectal cancer. The serum CA242 level of patients with lung cancer, liver cancer and ovarian cancer can be increased. CA72-4 is one of the best tumor markers for the diagnosis of gastric cancer, with high specificity and sensitivity up to 28-80%, if combined with CA19-9 and CEA, it can monitor more than 70% of gastric cancer. CA72-4 levels can rapidly decrease to normal after surgery. In 70% of recurrent cases, CA72-4 concentrations are first elevated. The main advantage of CA72-4 over other markers is its extremely high specificity for the differential diagnosis of benign lesions, with a detection rate of only 0.7% in a large number of patients with benign gastric disease. Colon/rectal cancer, pancreatic cancer, liver cancer, lung cancer, breast cancer and ovarian cancer also have a certain positive rate. 9, Ferritin (SF) Elevated ferritin can be seen in the following tumors: acute leukemia, Hodgkin's disease, lung cancer, colon cancer, liver cancer and prostate cancer. Detection of ferritin has diagnostic value for metastatic tumors of the liver. 76% of patients with liver metastases have ferritin levels higher than 400 μg/L. When liver cancer is present, the low value of AFP measurement can be supplemented by ferritin measurement to improve the diagnostic rate. Ferritin is also elevated in cases of hyperpigmentation, inflammation, and hepatitis. The elevation may be due to cell necrosis, blocked erythropoiesis or increased synthesis in tumor tissue. 10. Prostate-specific antigen (PSA) PSA is a glycoprotein synthesized by human prostate epithelial cells and secreted into the seminal plasma. PSA is mainly found in prostate tissue and does not exist in women. The level of PSA in normal male serum is very low, with a serum reference value of <4 μg/L; PSA is organ-specific, but not tumor-specific. The positive rate for the diagnosis of prostate cancer is 80%. Benign prostate disease is also seen with varying degrees of elevated serum PSA levels. Serum PSA measurement is a monitoring indicator for postoperative recurrence and metastasis of prostate cancer and for the observation of efficacy. It is present in the blood in two forms: bound PSA and free PSAF-PSA/T-PSA ratio is an effective indicator to differentiate prostate cancer from benign prostate disease. 11.Prostate acid phosphatase (PAP) elevated serum PAP of prostate cancer is an important indicator of prostate cancer diagnosis, staging, efficacy observation and prognosis. Prostatitis and prostate hyperplasia also have a certain degree of PAP increase. 12.β2-microglobulin (β2-MG) β2-microglobulin (β2-m) is expressed on the surface of most nucleated cells. It is mostly used clinically to diagnose lymphoproliferative diseases, such as leukemia, lymphoma and multiple myeloma. Its level correlates with the number of tumor cells, growth rate, prognosis and disease activity. In addition, it can be used to stage patients with myeloma based on this level. Serum β2-MG can be increased in renal failure, inflammation and various diseases. Therefore, increased serum β2-MG should be excluded due to certain inflammatory diseases or reduced glomerular filtration function. 13.Neuron-specific enolase (NSE) NSE is an isoenzyme of enolase, which is a tumor marker for small cell lung cancer (SCLC) with a positive diagnostic rate of 91%. It helps in the differential diagnosis of small cell lung cancer and non-small cell lung cancer (NSCLC). It is also valuable for the observation of the efficacy and recurrence monitoring of small cell lung cancer. The serum NSE concentration can be significantly increased in neuroblastoma and neuroendocrine cell tumor. Cytokeratin 19 (Cyfra21-1) Cyfra21-1 is a soluble fragment of cytokeratin-19. Cyfra21-1 is the preferred marker for non-small cell lung cancer, especially squamous lung cancer. Cyfra21-1 is also a good marker for breast cancer, bladder cancer and ovarian cancer, and is a good adjuvant for diagnosis and treatment monitoring. 15.Squamous cell carcinoma antigen (SCCA) is a tumor-associated antigen TA-4 extracted from cervical squamous epithelial cell carcinoma tissue, with a minimal serum content of <2.5 μg/L. SCCA is a tumor marker for squamous carcinoma, and is suitable for the auxiliary diagnosis, treatment observation and recurrence monitoring of cervical, lung squamous, esophageal, head and neck, and bladder cancer. 16.Nuclear matrix protein-22 (NMP-22) NMP-22 (NuclearMatrixProtein-22) is a component of the cytoskeleton. It is closely related to cellular DNA replication, RNA synthesis, regulation of gene expression, and hormone binding. In bladder cancer, a large number of tumor cells apoptosis and release NMP22 into the urine, and the urinary NMP22 can be increased 25-fold. With 10kU/mL as the threshold value, the sensitivity for the diagnosis of bladder cancer is 70% and the specificity is 78.5%. The sensitivity for the diagnosis of invasive bladder cancer was 100%. 17.α-L-amyloidase (AFU) AFU is another sensitive and specific new marker for the detection of primary hepatocellular liver cancer. The serum AFU activity of primary hepatocellular carcinoma patients is significantly higher than that of other types of diseases (including benign and malignant tumors). However, it is worth mentioning that there is some overlap between serum AFU activity measurements in some metastatic liver cancer, lung cancer, breast cancer, ovarian or uterine cancer, and even in some non-neoplastic diseases such as cirrhosis, chronic hepatitis and gastrointestinal bleeding, which are also mildly elevated. In order to improve the diagnosis rate of primary liver cancer, AFU should be measured simultaneously with AFP, which has a better complementary effect. Secondly, in order to improve the accuracy and detection rate of tumor markers in clinical diagnosis, we recommend the use of combined assays for some tumors. We summarize them into a table listed below (see the table below). Cancer is one of the major culprits of death from global diseases. According to statistics, there are 173 new cancer patients per 100,000 people worldwide and 110 per 100,000 people in China. Experts point out that 1/3 of all tumors can be prevented, 1/3 of tumors can be cured, and 1/3 of tumors can prolong life. At present, the diagnosis and treatment of cancer in developed countries are mostly in early stage, and some tumor markers are made mandatory for certain people (such as PSA, etc.). Therefore, the significance of tumor marker (TM) testing is summarized as follows: I. Tumor screening Tumor screening is to find suspicious people from asymptomatic people. Tumor marker test is an effective method for initial screening of tumors. It is often used for screening of high-risk groups. AFP: Screening for primary liver cancer. PSA: Screening for prostate cancer in men over 50 years old. High-risk HPV : Screening for cervical cancer. CA125+Ultrasound: Screening for ovarian cancer in women over 50 years of age. Abnormally elevated tumor markers without obvious symptoms and signs need to be reviewed and followed up. If it continues to increase, the diagnosis should be confirmed in time. Diagnosis Auxiliary diagnosis: The specificity of tumor markers is not strong enough, and the diagnosis of tumor cannot be confirmed solely based on tumor markers, but it can provide clues for further diagnosis. Differential diagnosis: Ben-Hur protein, AFP, HCG, PSA, etc. have characteristic cancer spectrum. Cannot be diagnosed locally: tumor markers lack tissue and organ specificity. Dynamic observation: progressive elevation of tumor markers has clear diagnostic significance; the elevation of markers in benign diseases is transient; the elevation of markers in malignant tumors is persistent. The most important clinical application of tumor markers is to monitor the efficacy and recurrence of metastasis. After surgery, chemotherapy or radiotherapy, there is a good correlation between the rise and fall of specific tumor markers and the efficacy of treatment, which can reflect the recurrence and metastasis of tumor through dynamic observation.