Malignant tumors seriously threaten the life safety and physical and mental health of the general public, and on April 29, 2008, the health department announced the results of the third cause of death survey in China: cancer is the second cause of death in China, accounting for 22.3% of the total number of causes of death, but in urban areas, cancer mortality has become the first cause of death. Compared with the two cause of death surveys in the 1970s and 1990s, the cancer mortality rate has increased by 83.1% and 25.5% respectively. The annual number of cancer deaths in China is >1.5 million; the number of new cancer cases is >2 million; the annual cost for cancer patients is about 100 billion, accounting for about 20% of the total national health cost. Early diagnosis is the key to cure tumors. At present, a variety of special examinations are clinically applied to expect to improve the early diagnosis rate of tumor, including X-ray examination, ultrasound examination, CT examination, magnetic resonance examination, endoscopy, etc.. These examinations can diagnose tumors from different angles and aspects, and each of them has its own limitations. The emergence of tumor marker (TM) has raised great hope for the early diagnosis of tumor. The detection of tumor markers is of great significance for the auxiliary diagnosis of tumors and the evaluation of prognosis, regression and efficacy of tumors. With the progress of molecular biology and human genome project, more and more specific tumor markers have been discovered and applied, providing a new way for the early diagnosis of tumors. However, many research reports have over-exaggerated the role of tumor markers and misled some clinical workers and the general public to understand the significance of tumor marker detection. It is significant to correctly evaluate the role of tumor markers and apply them reasonably in clinical work. Tumor markers are substances produced by tumor cells themselves or by the body’s reaction to tumor cells during the process of tumor development and proliferation, which reflect the existence and growth of tumor, including proteins, hormones, enzymes (isoenzymes), polyamines and oncogene products, etc. The Bence-Jones protein, discovered in 1846, was used for the detection of tumors in multiple bones. Jones protein was applied to the diagnosis of multiple myeloma in 1846, making it the first reported tumor marker. At present, more than 100 kinds of tumor markers with clinical significance have been discovered. The ideal tumor markers should have the following characteristics: (1) high sensitivity; (2) good specificity; (3) able to localize the tumor; (4) related to the severity of disease, tumor size or stage; (5) able to monitor the effect of tumor treatment; (6) monitor the recurrence of tumor; (7) predict the prognosis of tumor. However, so far, there is no “ideal” tumor marker. Due to the complexity of tumor genes, there is no single type of tumor, so it is very difficult to find the “ideal” tumor marker. The early detection of tumor is the basis for evaluating the effectiveness of tumor screening program. The detection method should be simple, safe, reliable and non-invasive to the body, with high sensitivity and specificity, accurate and reliable results, and few false positives and false negatives. The following principles should be considered when using tumor markers for screening: (1) The tumor markers have high sensitivity for the detection of early tumors. (2) The sensitivity, high specificity and good reproducibility of the measurement method. (3) The cost of screening is economic and reasonable. (4) The tumor marker is abnormally elevated during screening, but there are no symptoms and signs, which must be reviewed and followed up. However, in fact, there is no tumor marker with specificity and sensitivity of l00%, thus limiting the use of tumor markers for screening. Take colon cancer screening as an example, its incidence rate is 37/100,000, if a group of people are screened for colon cancer with carcinoembryonic antigen (CEA), the number of false positives is as high as 4,998, while only 26 colon cancer patients are detected, which causes a lot of wasted medical resources and examination costs. Therefore, this category of tumor markers is generally not suitable for screening of asymptomatic people. It has been confirmed that except for AFP, which helps to improve the screening and early diagnosis of liver cancer in high-risk groups of liver cancer, and PSA, F-PSA and their ratios, which help to diagnose prostate cancer at an early stage, other tumor markers are not of great significance for the early diagnosis of tumors, and their clinical value is mainly reflected in analyzing the efficacy, judging the prognosis, and predicting recurrence and metastasis. Although the sensitivity of many tumor markers can reach more than 80%, due to the heterogeneity of tumor, quite a number of patients do not have the expression of corresponding tumor markers in the process of tumor development, which leads many doctors and patients to face the negative result of tumor markers blindly and optimistically, without further adjuvant examination, which results in losing the good time for tumor treatment. As a result, they lost a good opportunity to treat tumors, causing many regrets. For example, the positive rate of tumor markers like AFP, which is quite significant for the early diagnosis of primary liver cancer, only reaches 79%-90% (the positive threshold of AFP for primary liver cancer diagnosis is >400ng/ml). That is to say, there are still 10%-30% of patients with primary liver cancer who have normal or only mildly elevated AFP. Therefore, in clinical work, doctors should be equally vigilant when facing negative reports of tumor marker results. They should carefully inquire into the medical history according to the patient’s specific situation, carefully conduct physical examination, and combine with corresponding auxiliary examinations to avoid unnecessary missed diagnosis. Most of the tumor markers can exist in malignant tumors and some benign tumors, inflammation, and even normal tissues, and there is no tumor marker with 100% specificity. For example, AFP may be elevated in patients with viral hepatitis and cirrhosis and pregnant women, CA19-9 values may be several times higher than normal in patients with obstructive jaundice or rheumatism, mild to moderate elevation of PSA in prostate hypertrophy and prostatitis, mild to moderate elevation of CA125 in endometriosis, and even mild elevation of CEA in long-term smokers. Therefore, the diagnosis of tumor cannot rely on the tumor marker test alone. A mild elevation of a single tumor marker or no major change in the results of each test is not clinically significant, but only a dynamic and continuous elevation is meaningful. The persistent elevation of a certain tumor marker or several tumor markers found in the physical examination should be alerted, and further examination by ultrasound, CT, MR, endoscopy or the most advanced PET/CT is needed, and if necessary, pathological examination is required to make a clear diagnosis. The change of tumor markers is very important to evaluate the treatment effect and judge the prognosis. If the tumor marker decreases from elevated to normal after surgery, it indicates successful surgery; if it does not or slightly decreases after surgery and then re-increases, it suggests that there may be tumor residue after surgery; if it decreases after surgery and then increases significantly after some time, it suggests tumor recurrence or metastasis. This indication often precedes the appearance of clinical symptoms by several months. The rise and fall of tumor markers can indicate the prognosis of tumor patients, and has guiding significance for the adjustment of treatment plan. A decrease in tumor markers after treatment indicates effective treatment; if tumor markers continue to rise after treatment, the treatment plan should be changed. If tumor markers continue to rise after changing the treatment plan, it often indicates recurrence or metastasis. Another point that clinicians should pay attention to is that the concentration of tumor markers measured immediately after chemotherapy, radiotherapy or surgery may have a transient increase, which is due to tumor necrosis, and the correct time to test is 6 weeks after treatment. V. Reasonable combined application of tumor markers Combined testing of multiple tumor markers can improve the sensitivity of diagnosis. Tumor is the result of multiple cloning of single mutated cells, and its occurrence is a multi-step and multi-gene cancer process. The biological characteristics of tumor cells are complex and polymorphic, and there are cells with very different biological characteristics in each tumor entity. The cell surface receptors, antigenic epitopes, expressed gene products, growth rate, infiltration, metastasis, and sensitivity to chemotherapy and radiotherapy may all be very different. These cells may not be identical in terms of synthesis, expression, and release of tumor markers. Therefore, the same tumor may contain one or more tumor markers, while different tumors or different tissue types of the same tumor may have both common and different tumor markers. In order to improve the positive rate of tumor marker detection, some tumor markers with higher specificity are selected for combined detection, which can improve the application value of tumor markers. The correlation between some tumor markers is extremely high, for example, the correlation between CA199 and CA50 can reach 95%-98%, that is, 95%-98% of the subjects with normal CA199, CA50 is also normal, CA199 is abnormal, CA50 is also abnormal. For example, CA242 is less affected by jaundice and has a higher value in the differential diagnosis of benign and malignant diseases of the biliary tract and pancreas. VI. Principles of regular follow-up of tumor markers Many clinicians do not understand the principles of follow-up of tumor markers, and the recommendations of follow-up of tumor markers for patients are also different. The expert committee of tumor markers of Chinese Medical Association Laboratory Medicine Branch suggests that after the treatment of malignant tumor is finished, the tumor markers elevated before the treatment should be monitored for regular follow-up according to the condition. The half-life of different tumor markers is different, so the time and period of monitoring is also different. Most domestic and foreign experts suggest that the first measurement should be done 6 weeks after treatment; every 3 months for 3 years; every 6 months for 3~5 years; and every year for 5~7 years. If a significant elevation is found during follow-up, it should be retested after 1 month. 2 consecutive elevations may indicate recurrence or metastasis. This prognosis is often earlier than clinical symptoms and signs, and helps clinical management in a timely manner.