Tumor Marker Testing

AFP (a-fetoprotein, a-FP AFP) 【Specimen collection】 2ml of venous blood, without anticoagulation, serum was isolated for determination. Normal reference value】 0-8.1ng/mL 【Project overview】 The clinical value of the tumor marker AFP is used to diagnose primary hepatocellular carcinoma and embryonic cell tumors in high-risk groups (cirrhosis, testicular swelling). Its main significance is to monitor the treatment and course of patients with hepatocellular carcinoma and embryonal cell tumors. The AFP molecule is a single polypeptide chain with a molecular weight of 70,000-71,000 and is mainly used in the diagnosis of primary hepatocellular carcinoma. AFP in the embryonic period functions as serum albumin and may also have a role in protecting the fetus from maternal rejection during the life of the fetus. After 1-2 weeks of life, with the cessation of placental hematopoiesis, the role of synthetic AFP is gradually reduced to normal. In normal individuals, the AFP synthesis gene is blocked in normal cells as a result of genetic factors. In patients with primary hepatocellular carcinoma and other tumors, the gene is activated in the corresponding tumor cells, resulting in the production of large amounts of AFP, which increases its concentration in the blood. Clinical significance】 1. Diagnosis and differential diagnosis of primary hepatocellular carcinoma. When AFP 200ug/L for 8 weeks, ALT is normal and pregnancy and germ cell malignancy are excluded, the diagnosis of primary hepatocellular carcinoma is tended to be made, with a positive rate of more than 80%. 2. A few cases of cirrhosis also have increased AFP, but they are all transient elevation, and the duration is mostly less than 2 months. 3.Some malignant tumors of reproductive system and gastrointestinal tract, especially when mixed with liver metastasis, AFP is also not increased. After surgical resection or interventional treatment, AFP should be reduced to below 25ug/L. If it is not reduced much or reduced but recurred, it indicates that surgical resection is not clean or there is a possibility of local recurrence. 5.The AFP of ovarian endodermal sinus cancer in obstetrics and gynecology is obviously elevated, which is not only used for diagnosis, but also for efficacy observation and prognosis judgment. 6.It is used to distinguish normal pregnancy from choriocarcinoma, the latter is not increased, pre-term abortion is decreased, and the prognosis of bad abortion is high AFP. Carcinoembryonic antigen (CEA) [Specimen collection] 2ml of venous blood, no anticoagulation, isolated serum for determination. Normal reference value】 0-15ng/mL 【Project overview】 CEA is a glycoprotein with 50% carbohydrate. The molecular weight of CEA isolated from colorectal cancer or cultured clonal cancer cells is 180 kDa. CEA is a normal component of colorectal mucosal glands and is also present in other epithelial such as vaginal epithelium and glandular tissues such as gastric lesser curvature and sweat glands. In colorectal mucous glands, CEA synthesis increases during 8-16 weeks of pregnancy and remains stable thereafter. Since CEA is a normal component of all types of epithelial cells and its synthesis is not higher in embryonic tissues than in adult tissues, the term “cancerous embryo” is incorrect. The highest concentrations of CEA are mainly found in primary colorectal cancer and its liver metastases. CEA is also elevated in other tumors such as stomach, breast, and lung cancers, but is significantly lower in lung cancer than in colorectal cancer. At the mRNA level, CEA expression in normal colorectal mucosal glands is not significantly different from that in colorectal cancer. However, why CEA is higher in colorectal cancer than in other normal mucosal tissues is still not fully explained. One reason is that there may be residual CEA-positive cells in the glands of the tumor, or it may be due to uncontrolled expression of the CEA family in colorectal cancer. Due to the mutual reaction between different families, the unstable synthesis between different families of CEA aggregates due to mutual reaction. [Clinical significance] The average CEA concentration in the serum of older or smokers is slightly higher than that of younger or non-smokers. In non-malignant cases, the following diseases can often cause increased CEA: hepatitis, alcoholic cirrhosis, pancreatitis, colorectal inflammatory diseases such as ulcerative colorectitis, diverticulitis and pneumonia. CEA is of limited value for differential diagnosis because of the high rate of positivity in patients with non-malignant disease that clinically resembles colorectal cancer. In pancreatic cancer, CEA is usually abnormal in advanced stages, and CA199 is superior to CEA. serum CEA concentrations are elevated in most patients with medullary thyroid cancer, and calcitonin is more sensitive and specific when measured after the pentagastrin provocation test. In some other primary tumors without metastasis, CEA is not suitable for differential diagnosis due to the limitation of sensitivity and specificity. In the differential diagnosis of liver tumors, CEA can be used as an additional tool in addition to imaging studies, especially when measured serially. About half of the patients with colorectal cancer and pancreatic cancer with liver metastases have serum CEA levels 8-10 times higher than the upper limit of the reference range, and 6% of patients with primary liver cancer have CEA concentrations up to this level. This is rarely seen in non-malignant liver disease. Measurement of CEA in colorectal cancer as a prognostic indicator can also be used to diagnose the presence of residual cancer tissue after surgery. Within a certain tumor stage (TNM stage), preoperative CEA concentration can be used as a predictive value. Generally speaking, tumors with high CEA concentration have a poor prognosis. To distinguish whether the increased CEA is caused by primary tumor or distant metastasis, it can be determined by measuring CEA continuously (every 6-8 weeks after surgery) during postoperative follow-up. A postoperative CEA that does not fall within the reference range but instead rises is highly predictive of possible residual cancerous tissue. Cancer antigen 125 (CA125) [Specimen collection] 2ml of venous blood without anticoagulation, serum was separated for measurement. CA125 is a monoclonal antibody obtained by Bast et al. in 1983 by immunizing BALB/c mice with ovarian plasmacytoid cystic carcinoma cell line OVCA433 by hybridization with myeloma cells, and the antigen recognized by this antibody is called CA125. It is unstable and has a molecular weight between 200,000 and 1,000,000. It has important diagnostic value for ovarian and reproductive system tumors, and also has good reference value for the diagnosis of pancreatic, lung, liver and rectal cancers. CA125 is very low in normal human tissues. the main use of CA125 is to assist in the diagnosis of ovarian cancer, estimate the efficacy and monitor the course of the disease; it can also be used as a secondary marker for the diagnosis of pancreatic cancer after CA19-9. However, it has low clinical sensitivity and specificity for other malignant diseases. Clinical significance】 CA125 is suitable for treatment evaluation and disease course monitoring of patients receiving treatment for ovarian cancer. Postoperative CA125 levels correlate with tumor volume and can be used as a prognostic indication for clinical presentation. The risk of recurrence has been reported to be highest in patients with CA125 above 35 U/mL. According to the literature, patients with CA125 levels greater than 35 U/mL prior to second-look surgery are likely to have tumors present at the time of surgery or to have recurrent disease later. However, a CA125 level less than 35 U/mL prior to second-look surgery does not establish that the patient does not have residual tumor. CA125 levels measured after second-look surgery provide a fairly valid clinical indication. The rate of change in CA125 is also highly prognostic. a rapid decrease in CA125 levels suggests that the patient is responding positively and well to treatment. Elevated CA125 levels after the third course of initial chemotherapy are indicative of a poor prognosis. As a diagnostic method, CA125 levels alone are not sufficient to determine the presence or extent of disease. Pre-surgical CA125 levels in patients with malignant pelvic masses do not suggest any information regarding mass diameter or histologic grading. However, in postmenopausal female patients, a combination of ultrasonography and CA125 level testing can distinguish between benign and malignant pelvic masses. Certain patients in benign disease states (e.g., cirrhosis, acute pancreatitis, endometriosis, pelvic inflammatory disease, menstruation, first trimester of pregnancy) may also have elevated CA125. Elevated CA125 levels have also been found in 1-2% of healthy blood donors. Cancer antigen15-3 (CA15-3) [Specimen collection] 2ml of venous blood, without anticoagulation, serum isolated for determination. Normal reference value】 0-32.4U/mL 【Project overview】 CA153 is a valuable indicator for monitoring the disease course of metastatic breast cancer patients. It is not suitable as a screening and diagnostic indicator because the clinical sensitivity of CA153 assay for localized lesions is too low, and there are a considerable number of patients with elevated CA153 levels in benign breast disease and cancers of other organs. [Clinical significance] CA153 is a highly concentrated polymorphic glycoprotein, belonging to the mucin class, and is a MUC-1 gene product. Metastatic breast cancer is usually associated with cancer-related circulating antigens (e.g. CA153). In industrialized countries, 1 in 10 women is expected to be diagnosed with breast cancer at some point in their lifetime. In the United States, there were an estimated 184,600 new cases of breast cancer in 1997 and an estimated 44,700 breast cancer deaths. Most women with a recent diagnosis of breast cancer disease show only limited lesions (5-year survival rate is 96%), and 42% of women diagnosed with breast cancer have extramammary disease; for these women, the 5-year survival rate is 76% for women with limited lesions and 20% for women with distal metastases. Most breast cancer deaths are caused by disease progression and spread. Although numerous treatments are available for breast cancer, most breast cancers usually have no specific drugs and require second- and third-line therapeutic control. The use of circulating tumor markers (e.g., CA153), which can monitor treatment response and indicate the aforementioned disease status, is an effective means of treating the above patients. Since there is a direct relationship between changes in CA153 levels and clinical status, monitoring the disease process and treatment response by serial measurement methods is the most effective means. A decrease in CA153 levels in patients with known metastases indicates effective treatment; conversely, an increase in CA153 levels indicates resistance to treatment and progression of disease, requiring further clinical evaluation and normal surveillance. Recently it has been shown that when there is no clinical evidence of disease and the patient’s CA153 level is elevated above the upper limit of normal, it is an early indication of disease recurrence. In sera from patients with stage II and III breast cancer in symptomatic remission, elevated CA153 levels provided a positive predictive value of 83.3% for recurrence, with an average lead time of 5.3 months before clinical determination of disease recurrence. Carbohydrate antigen 19-9 (CA19-9) [Specimen collection] 2 ml of venous blood, without anticoagulation, and isolated serum for determination. CA199 is an oligosaccharide related to sialic acid lactate N pentose II, a mucin-like component of serum from tumor patients, with a molecular weight of 5 million and a minimal content at 37℃ for 5 hours under alkaline conditions. CA199 is neither a tumor-specific nor an organ-specific antigen, and it is mainly used for early diagnosis, treatment and monitoring of patients with pancreatic, hepatobiliary and gastric cancer. It is mainly used for early diagnosis, monitoring of treatment and detection of cancer recurrence. Clinical significance】 CA199 is a tumor-associated antigen that reacts with antibodies produced by immune response in human colon cancer cell lines. Although the antibody is derived from a colon cancer cell line, studies have shown that CA199 is more effective than colon tumors in the diagnosis and treatment of pancreatic tumors. CA199 is also a more sensitive and specific marker for pancreatic cancer compared to other serological markers. While very few antigens are found in the blood of normal patients or patients with benign disease, most patients with pancreatic cancer show elevated levels of CA199. Although elevated CA199 levels are not a prominent feature of pancreatic cancer, the CA199 test is currently the single most effective blood test for differentiating benign pancreatic disease from malignant pancreatic disease. When CA199 testing is combined with imaging analysis (such as ultrasonography or computed tomography [CT]), a higher diagnostic sensitivity is obtained. This combination is indicated for the diagnosis of patients suspected of having pancreatic cancer (despite a “negative” or “inconclusive” result on imaging analysis). The success of pancreatic resection and prognosis after surgery can be evaluated using serum CA199 levels, and Steinberg found that in patients with CA199 levels greater than 1000 U/mL, 96% of tumors were not feasible for surgery. Patients with normal CA199 levels after surgery survived longer than those with abnormal levels. Serially measured CA199 levels can be used to predict disease recurrence prior to radiographic or clinical findings. CA199 can also be used to detect bile duct, hepatocellular, gastric, colonic, esophageal, and non-gastrointestinal tumors (but this area is increasingly less used.) CA199 is still most effective as a marker for pancreatic cancer. Prostate specific antign (PSA) [Specimen collection] 2ml of venous blood, no anticoagulation, serum isolated for determination. PSA is immunologically different from prostatic phosphatase (PAP) and does not have the function of hydrolyzing phosphate, its physiological role is not fully understood. The PSA is produced in the epithelial cells of the prostate gland and is only found in normal human serum at very low levels. The PSA level in the serum has some clinical value for the prognosis of the disease. When the disease is in remission, the blood PSA level decreases, and when the disease deteriorates, the PSA level increases. Chronic prostatitis and simple prostate hypertrophy can sometimes appear mildly elevated, at this time should be closely combined with clinical, comprehensive judgment. The PSA level can be increased by a combination of the antigen and the antigen. PSA is a neutral serine protease containing 240 amino acids, which is involved in the breakdown of semen clots. PSA is complexed with a variety of protease inhibitors and is found primarily in the circulatory system. The most common form of detectable compound PSA (cPSA) is bound to ACT (alpha-1-antitrypsin). When applied in combination with other diagnostic indices, cPSA is effective in identifying residual tumor and early recurrence after treatment. Patients with prostate cancer have elevated cPSA levels, which usually drop to very low levels after radical prostatectomy. Clinical significance】 CPSA can assist in the clinical diagnosis of prostate cancer and the observation of patient outcomes. The elevated serum levels precede the clinical diagnosis by 3-5 years and can be detected in 63-71% of patients with focal organ cancer, compared to 33% with cystoscopy. 80% of patients with prostate cancer detected by the cPSA screening test have clinical signs, and the patient’s life is already threatened and treatment needs to be provided. He II tumor protein HER-2/neu 【specimen collection】 2ml of blood was collected intravenously and the serum was separated for determination. Normal reference value] Chemiluminescence method: <12.7ng/ml. [Project review] HER-2/neu oncogene (erB-2) encodes a protein with a molecular weight of 185,000 daltons (p185). This oncogene belongs to the genus of cell surface receptors for tyrosine kinase activity in giant cells and has some structural correlation with the endothelial growth factor receptor (erB-1). HER-2/neu oncogene is composed with other protein regions, transmembrane region and extracellular region (ECD). In the mid-1980s, HER-2/neu oncogenes with their protein products have been reported to have an important role in the development and metastasis of breast cancer. ECD exposed outside the cell has been found to be a glycoprotein, usually p105, with a molecular weight between 97-115 daltons. Numerous reports have shown that ECD is seen in the blood of normal individuals and appears elevated in the blood of patients with metastatic breast cancer. In addition, HER-2/neu protein is overexpressed in various other tumor types of epithelial origin, including lung, hepatocellular, pancreatic, colon, gastric, ovarian, cervical, and bladder cancers. HER-2/neu is a tumor protein directly related to the biology of cancer. 25-30% of women with breast cancer show overexpression of HER-2/neu. HER-2/neu is important in the process of carcinogenesis, and overexpression of HER-2/neu in serum is an indication of poor prognosis. The higher the level of HER-2/neu, the more rapid the malignant transformation and the greater the tumor load. For breast cancer patients with HER-2/neu overexpression, Herceptin should be used for treatment. Myocardial marker assay Creatine kinase isoenzyme (CK-MB) [Specimen collection] 2ml of blood was collected intravenously and serum was separated for measurement. Normal reference value】 Chemiluminescence method: 〈5.0ng/ml 【Project review】 CK is known to contain two subunits, and M and B. From these two subunits, three isoenzymes are combined, namely CKMM, CKBB and CKMB. 【Clinical significance】 CKMB exists almost exclusively in the myocardium, and is a more sensitive and specific indicator of myocardial injury compared to total CK. In brain and skeletal muscle diseases, CKMB is not elevated. With open heart surgery, intramuscular drug injection, trauma, shock due to non-myocardial infarction, stroke, tumor and hypothyroidism, total CK can increase up to 20-fold of normal, while CKMB is not elevated. Therefore, in patients with suspected acute myocardial infarction, CKMB measurement provides one of the most accurate enzymatic indicators. A significant increase in MB indicates a large myocardial infarction and a poor prognosis. Myoglobin (MYO) [Specimen collection] 2ml of blood was collected intravenously and the serum was separated for measurement. Normal reference value】 Chemiluminescence method: <110ng/ml. Myoglobin, with a molecular weight of 17,500, is a monomeric hemoglobin unique to transverse muscle tissue and is found in very small amounts in normal human serum. Therefore, serum myoglobin measurement is commonly used as an early diagnostic indicator of acute myocardial infarction. Myoglobin is a low molecular pigment protein containing ferrous hemoglobin, which is produced in cardiac and skeletal muscle. Its ferrous hemoglobin is reversibly bound to oxygen and functions locally to store and transport oxygen. The content of myoglobin in myocardial tissue is 1.4mg/g myocardium, in skeletal muscle myoglobin accounts for 0.1-0.2% of the total muscle protein, and smooth muscle cells do not contain myoglobin. Clinical significance】 In acute myocardial infarction, myocardial ischemic necrosis occurs and cell permeability increases. Since the molecular weight of myoglobin is only 17,500, which is much smaller than enzyme molecules such as CKMB and AST, it is more easily released into the blood circulation, thus becoming the earliest diagnostic indicator of acute myocardial infarction. In general, myoglobin starts to rise 1-3 hours after the onset of acute myocardial infarction, reaches its peak planting in 4-12 hours, myoglobin can be 7 times higher than normal, starts to fall in 12 hours, and returns to approximately normal in 24 hours. Therefore, the positive rate of this item for acute heart attack can reach 92%, while the positive detection rate after 24 hours is only 40%. Myoglobin can also be used as a monitoring indicator of reperfusion after thrombolytic therapy in patients with myocardial infarction. Successful reperfusion is indicated if the concentration of myoglobin exceeds four times the pre-thrombolysis level within 1-2 hours after thrombolysis. Troponin I (cTnI) [Specimen collection] 2ml of blood was collected intravenously and the serum was separated for measurement. Normal reference value】 Chemiluminescence method: 〈1.5ng/ml 【Project overview】 Troponin exists on the double helix structure of pro-troponin of transverse muscle fine filaments, and is a complex of three single chain polypeptides: troponin I (myosin ATPase inhibitory unit), troponin C (calcium ion binding unit) and troponin T (pro-troponin binding unit), troponin is associated with sarcoplasmic calcium ion, and prothymosin together regulate muscle contraction. There are three types of troponin I: cardiac, slow-contracting skeletal muscle, and fast-contracting skeletal muscle, and each type has its own specific amino acid sequence and gene code. Cardiac troponin I has 26 additional amino acid residues at the N-terminal end that are not present in the skeletal muscle type. Therefore, cTnI is 100% cardiac specific. The degree and duration of cTnI elevation is positively correlated with the degree of myocardial injury and the area of necrosis. The rise in cTnI level after infarction appears later than myoglobin and is similar to CKMB, but the time to return to basal level is much longer than myoglobin and CKMB, which is valuable for differential diagnosis of patients who have passed the peak at the time of admission and atypical patients. Serial testing of cTnI is helpful in determining thrombolysis and myocardial reperfusion. Homocysteine (HCY) 【Specimen collection】 2ml of blood was collected intravenously and the serum was separated for measurement. Normal reference value】 Chemiluminescence method: 〈5.0-13.9umol/L 【Project overview】 About 70% of homocysteine in plasma is bound to albumin, which is the bound type. The remaining free type is important in the form of disulfide homocysteine and disulfide-bonded homocysteine-cysteine compounds, and only a small amount exists in plasma in the form of reduced homocysteine. Clinical significance] In recent years, homocysteine has been used in clinical practice mainly as a risk indicator for cardiovascular diseases, especially coronary atherosclerosis and myocardial infarction, and its elevated concentration is directly proportional to the risk of the disease. In addition, according to the metabolic characteristics of homocysteine, VB12p folate deficiency and hereditary N5methyltetrahydrofolate transmethylesterase p cystathione-β-synthase gene defect also have a close relationship with homocysteine concentration, but the connection between these factors and cardiovascular diseases needs further study. 1.In the past, it was mainly used for the detection and treatment of homocysteinuria and homocysteine hyperemia. 2.Now it is used for risk assessment of cardiovascular disease. 3, Recent studies have attempted to explore the relationship between increased HCY levels and the risk of developing progeria p dementia and nerve duct deficiency disease and mortality. 4, The possible combined effect of HCY and the coexistence of multiple other risk factors on the disease. In 1999, the American Heart Association recommended screening for HCY in high-risk groups.