Tumor markers were first introduced in 1978 by Herberman at the National Cancer Institute’s conference on “Immunodiagnosis of Human Tumors”. The following year, it was confirmed by the participants of the 7th Conference on Oncogenesis Biology and Medicine in the UK and started to be quoted publicly. Tumor markers are substances, including proteins, hormones, enzymes (isoenzymes), polyamines and oncogene products, which are synthesized and secreted by the gene expression of tumor cells or produced and/or elevated by the body in response to tumors during the process of malignant tumorigenesis and proliferation, reflecting the presence and growth of tumors. Tumor markers are present in the blood, body fluids, cells or tissues of patients and can be measured by biochemistry, immunology and molecular biology, which are valuable for tumor screening, diagnosis, efficacy observation, recurrence monitoring and prognosis evaluation. There is no universally accepted standard for the classification of tumor markers. Tumor markers are classified according to their chemical properties: 1) embryonic tumor antigen markers 2) glyco-antigen markers 3) protein tumor markers 4) hormone markers 5) enzymes and isoenzymes 6) receptor and viral tumor-associated antigens 7) gene markers. With the progress of tumor treatment, individualized tumor treatment is getting more and more attention, and the research of tumor markers is also getting more and more in-depth. For example, the study of EGFR mutation in lung cancer patients, the study of tumor VEGF, the study of KRAS mutation in colorectal cancer, the study of her-2 in gastric cancer and breast cancer, and so on. These play a very crucial role for the targeted treatment of tumors. However, it is difficult to carry out the above tests universally due to the limitations of many conditions such as specimens and tests. At present, serum tumor markers are still the main clinical tests for tumor screening, diagnosis, efficacy observation, recurrence monitoring and prognosis evaluation, because they are simple and easy to perform and can be repeatedly tested. The following are the clinical significance of several common serum tumor markers: a. Carcinoembryonic antigen (CEA) is one of the most commonly used tumor markers in clinical practice. Carcinoembryonic antigen was first discovered by Gold and Freedman from fetal and colon cancer tissues in 1965. In general, CEA is synthesized from fetal gastrointestinal epithelial tissue, pancreatic and hepatocytes. CEA levels are usually elevated during the first 6 months of pregnancy and are already low in serum after birth. Most of the CEA-secreting tumors are located in the epithelial tissues of cavernous organs, such as the digestive tract and respiratory tract. Such as colorectal cancer, gastric cancer, lung cancer, pancreatic cancer, breast cancer, ovarian cancer, etc. all see elevated serum CEA levels. Clinical significance of CEA: 1) Diagnosis of malignant tumors: many tumors such as colorectal cancer, lung cancer, pancreatic cancer, breast cancer, ovarian cancer, etc.; 2) Prognosis assessment of malignant tumors: normal preoperative CEA has a high cure rate and is less likely to recur after surgery. If the CEA is elevated before surgery, there are mostly vascular, lymphatic and perineural invasion and metastasis, which indicates poor prognosis. 3. Assessment of tumor treatment effect and recurrence: 50% to 60% of patients with postoperative lung cancer were found to have elevated serum CEA 4 weeks before the recurrence was confirmed by imaging diagnosis or after treatment. To determine the efficacy of surgery for colon cancer patients, CEA generally decreases to normal 1-6 weeks after surgery. 4. Non-tumor CEA elevation: smokers, ulcerative colitis, pancreatitis, colon polyps, active liver disease, etc. But the index is usually not too high. However, the index is usually not too high. AFP is another kind of tumor embryonic protein. AFP was found in fetal serum as early as the 1950s, and in the 1960s it was discovered that AFP was also present in the serum of people or animals suffering from primary liver cancer, after which it was gradually used for clinical diagnosis of liver cancer. AFP is a tumor marker for hepatocellular carcinoma, yolk sac tumor, embryonal carcinoma and germ cell tumor. clinical significance of AFP: 1. used for clinical diagnosis of primary liver cancer: in 1990, the National Office of Tumor Control and Prevention and the Chinese Anti-Cancer Association co-edited the “Chinese Common Malignant Tumor Diagnosis and Treatment Specification – Primary Liver Cancer”. -Primary hepatocellular carcinoma‖ provides the following clinical diagnosis of hepatocellular carcinoma: (1) If there is no other evidence of hepatocellular carcinoma, positive AFP by convective method or ≥400µg/L by radioimmunoassay for more than 4 weeks, and pregnancy, active liver disease, germinal gland embryonic-derived tumor and metastatic hepatocellular carcinoma can be excluded. (2) Those who have obvious hepatic substantial occupying lesions on imaging, can exclude hemangioma and metastatic hepatocellular carcinoma, and have one of the following conditions: ① AFP ≥ 200µg/L; ② typical imaging manifestations of primary hepatocellular carcinoma; ③ no xanthogranuloma but significantly elevated ALP or GGT; ④ clear distant metastatic lesions or bloody ascites, or cancer cells found in ascites; ⑤ clear hepatic sclerosis with positive hepatitis B or C markers. 2.For the observation of hepatocellular carcinoma efficacy and evaluation of prognosis: AFP should be reduced to normal in 2-4 weeks for completely resected hepatocellular carcinoma, otherwise it should be investigated for residual or metastatic tumor. 3.Stomach, esophageal, pancreatic, gallbladder, lung and breast cancers can also produce AFP, among which stomach cancer is the most common, especially those with liver metastasis. 4.Non-tumor AFP elevation: seen in pregnancy, active hepatitis, etc. The AFP can be increased in pregnancy and active hepatitis. CA15-3 was discovered in 1982 and 1984 by using two monoclonal antibodies one after another. The clinical significance of CA15-3: 1. The concentration of CA15-3 in the serum of breast cancer patients is often elevated, so CA15-3 is generally used as the main marker of breast cancer in clinical practice. The level of CA15-3 is positively correlated with the changes of breast cancer and is an important signal of recurrence and metastasis. If its serum level continues to rise, it should be closely monitored. In one of my patients, CA15-3 was found to be higher than normal by about 20U two years after breast cancer surgery, and no tumor recurrence was detected by various tests. Two years after the liver metastasis surgery, the patient showed elevated CA15-3 again, and three metastases in the liver were found by PET-CT in our hospital. After local and systemic chemotherapy, the patient is still alive and well, and this patient’s long-term survival is attributed to the detection of CA15-3.2. CA15-3 is also seen in other diseases such as liver, pancreatic, bile duct, stomach, lung, and ovarian cancers. CA15-3 is also sensitive to some benign lesions of the lung and liver, especially cirrhosis, hepatitis and other viral infections, and the positive rate is generally less than 10%. CA125 antigen was reported in 1983, CA125 is generated by tissues including peritoneum, fallopian tubes, endometrium, pleura, etc. Clinical significance of CA125: 1. 90% of CA125 values exceed normal in advanced ovarian cancer and 50% exceed normal values in early stage. In the treatment of ovarian cancer, if the patient’s CA125 value remains high after three cycles of chemotherapy, chemotherapy should be stopped unless there is a better chemotherapy regimen.2. Other non-ovarian malignant tumors also have a certain positive rate, such as breast cancer 40%, pancreatic cancer 50%, gastric cancer 47%, lung cancer 44%, colorectal cancer 32%, and other gynecological tumors 43%.3. Non-malignant tumors, such as endometriosis Although there are different degrees of elevation in non-malignant tumors, such as endometriosis, pelvic inflammatory disease, ovarian cyst, pancreatitis, hepatitis and cirrhosis, the positive rate is low. V. CA19-9 is a glycolipid. The clinical significance of CA19-9: 1. Diagnosis of pancreatic cancer: Most patients with pancreatic cancer have significantly higher serum CA19-9 levels; CA19-9 levels are related to the stage of the tumor, so the level of serum indicates the ease of surgery. Therefore, the level of CA19-9 in the serum indicates the ease of surgery; the preoperative CA19-9 level has a suggestive effect on the prognosis, and those who have a low level have a better prognosis; those whose CA19-9 level decreases to normal after surgery have a longer survival than those who do not; CA19-9 can increase again when the tumor recurs, and it occurs before the imaging diagnosis. Therefore, CA19-9 can be used to monitor the recurrence of tumors.2 CA19-9 is also elevated to different degrees in cancers of the hepatobiliary system (49%), stomach (67%) and colon (58%). CA19-9 is usually 100u/ml in benign diseases such as cholecystitis, pancreatitis and obstructive jaundice, but it is often a “transient” increase. Urine periprotein is the earliest tumor marker discovered. It was first described by Henry Bence Jones in 1845 and proved to be a light chain component of immunoglobulin in 1963. The detection of periprotein has now been superseded by the detection of the light chain component in blood and urine. It is mainly used for the diagnosis of multiple myeloma. VII. Neurospecific enolase (NSE) is an acidic protease involved in glycolysis, with the main role of catalyzing the conversion of 2-phosphoglycerol into enolpyruvate. Enhanced glycolysis in tumor tissues, accelerated cell proliferation cycle, and increased release of intracellular NSE into the blood lead to increased levels of this enzyme in the serum. The positive rate of serum NSE detection in patients with small cell lung cancer (SCLC) can be as high as 65%-100%, and it is currently believed that NSE can be used as a highly specific and sensitive tumor marker for SCLC. The serum NSE level reflects the response to chemotherapy. A temporary increase in NSE (tumor dissipation phenomenon) may occur 24 to 72 hours after treatment, which is the first sign of effective treatment. Patients who respond well to chemotherapy generally show a rapid decrease in serum NSE levels within 1 week after the first course of treatment. PSA: It was first discovered by Hara in 1971 to be synthesized by prostate epithelial cells and secreted into the semen. PSA is a marker protein of prostate epithelial cells and is found only in the prostate alveoli, urethral duct epithelium and semen, not in other tissues or in non-prostate malignancies. 1995 FDA approved serum PSA testing as a prostate screening indicator in older men. It is currently one of the most sensitive tumor markers in prostate cancer, and PSA can be used to detect and diagnose prostate cancer, as well as to monitor treatment. PSA values are closely related to the stage of prostate cancer; it should be noted that under normal circumstances, PSA levels rise with increasing age of the patient. Rectal examination of the prostate, endourethral instrumentation, and intraluminal ultrasound can cause a transient increase in serum t-PSA levels. It is suggested that fingerprick, biopsy, intraurethral instrumentation, intraluminal ultrasound, and prostate massage should be avoided 48 hours prior to PSA blood collection. ix. CYFRA 21-1 is a fragment of cytokeratin 19. CYFRA 21-1 is the most sensitive tumor marker for NSCLC. The normal value is Q3.3 ng/ml. the level of CYFRA 21-1 in serum is positively correlated with the disease duration of patients with squamous lung cancer, and the sensitivity of patients with stage I-IV is 60.0%, 88.8%, 80% and 100%, respectively, according to the TNM stage of lung cancer. CYFRA 21-1 is also a useful bladder tumor marker, not only for diagnosis, but also for follow-up. It can also be valuable as a follow-up, especially for predicting the recurrence of bladder cancer. How to select and apply tumor markers rationally: clinically, due to the heterogeneity of tumors, one tumor can express multiple tumor markers; one tumor marker can be expressed in multiple tumors. In addition, the current tumor markers are not unique to tumor tissues, they can be expressed in non-tumor conditions, only the amount of expression is different. Therefore, most of the tumor markers are of limited diagnostic value for tumor diagnosis. However, for patients with confirmed tumors, tumor markers are of great importance for observation of efficacy, monitoring of recurrence and prognosis. The selection of tumor markers for tumor patients should be done before treatment, such as before surgery, radiotherapy and chemotherapy. According to the possible tumors, multiple markers should be selected for combined testing, avoiding empirical testing so as not to miss the most valuable markers. For example, patients with gastric cancer may express AFP, etc. in addition to CEA and CA199 frequently. Be sure to choose the marker with the highest serum concentration as the monitoring index before surgery or treatment, and combine multiple markers if necessary. After the tumor markers are determined, establish the patient’s baseline measurement value and draw a graph of the patient’s tumor marker level, which is helpful for judging the efficacy and monitoring the recurrence. Two consecutive increases or decreases of 25% during the treatment period are considered to have clinical value, but errors caused by the measurement method must be excluded. After the first increase in the measured value, a review should be performed within 2-4 weeks. After the end of treatment, in addition to regular follow-up examinations, tumor markers should be tested. The first measurement is usually done 6 weeks after treatment; every 3 months for the first 3 years; every 6 months for 3-5 years; and every year for 5-7 years. If there is a large linear increase in the value of tumor markers for more than 3 consecutive times during the treatment period, the recurrence of tumor lesions should be noted.