Tumor marker (tumormarker, TM) refers to a substance that can reflect the existence and growth of a tumor, either synthesized and secreted due to the gene expression of tumor cells or abnormally produced and/or elevated due to the body’s response to the tumor in the process of malignant tumor development and proliferation.

This article summarizes 49 tumor markers of 13 major cancer types, and the detailed understanding of tumor markers of major cancer types is as follows.

01. Common TMs

CEA (Carcinoembryonic Antigen)
Normal range: 0-5ng/mL; CEA is a traditional non-specific, broad-spectrum tumor marker, with a detection rate of over 80% in lung adenocarcinoma. Diseases such as colorectal cancer, pancreatic cancer, gastric cancer, breast cancer, etc. also show elevated CEA index. In the diagnosis of malignant tumors, identification of disease, monitoring the evaluation of the efficacy of treatment, CEA test has a relatively important clinical value. And the level of CEA is also correlated with the stage of cancer, the more advanced the tumor, the higher the value of CEA. If metastasis occurs, its concentration will also be elevated.
CA125 (Glyco Antigen 125)
Normal range: 0-35 U/mL; this indicator is often seen to be elevated in malignant tumors, such as ovarian epithelial cancer, fallopian tube cancer, endometrial cancer, lung adenocarcinoma, and gastrointestinal adenocarcinoma, etc. Therefore, when this indicator is found to be higher than normal, chest and abdominal CT should be improved to clarify whether the disease is present. However, it is not a diagnostic indicator of malignant tumors. Elevated CA125 can also be seen in benign diseases, such as large amount of ascites, benign ovarian tumors, and so on.
CA19-9 (Glycoantigen 19-9)
Normal range: 0-37U/mL; CA19-9 is obviously elevated in pancreatic cancer, gallbladder cancer, bile duct jugular cancer, especially in the advanced stage of pancreatic cancer, the positive rate can reach 75%, and it is an important auxiliary diagnostic index.The positive rate of CA19-9 in gastric cancer is 50%, that of colorectal cancer is 60%, and that of hepatocellular carcinoma is 65%. Other malignant tumors also have a certain positive rate, such as: breast cancer, ovarian cancer, lung cancer and so on. In addition, CA19-9 is also elevated to varying degrees in certain inflammatory diseases of the digestive tract, such as: acute pancreatitis, cholecystitis, cholestatic cholangitis, hepatitis, cirrhosis, and so on.
CA15-3 (glycan antigen 15-3)
Normal range: 0-32.4 U/mL; early sensitivity of breast cancer is up to 60%, late sensitivity is up to 80%, postoperative follow-up and recurrence of metastasis are of great significance. dynamic measurement of CA15-3 is helpful for the early detection of recurrence after treatment in patients with Stage II and Stage III breast cancer; metastatic lesions can be considered to be present when CA15-3 is greater than 100 U/ml. Other malignant tumors also have a certain positive rate, such as: lung cancer, colon cancer, pancreatic cancer, ovarian cancer, uterine cervix cancer, primary liver cancer and so on.
SCC (Squamous Epithelial Cell Carcinoma Antigen)
Normal range: 0-1.5 μg/L; it is a valuable tumor marker for early diagnosis, treatment observation and recurrence monitoring of cervical cancer, lung squamous carcinoma, esophageal cancer, head and neck cancer, bladder cancer and other diseases.
NSE (neuron-specific enolase)
Normal range: 0-16.3 ng/mL; as an important tumor marker in SCLC, its detection rate in SCLC is 91%, and it can be used as an important indicator for SCLC treatment effect and recurrence monitoring. Serum levels of NSE were also significantly higher in patients with neuroblastoma and neuroendocrine cell tumors.

02. Lung cancer serum TM

Pro-GRP (gastrin precursor releasing peptide fragment)
The serum TM Pro-GRP (gastrin precursor releasing peptide fragment) is highly specific for the diagnosis of SCLC when it is higher than 24 ng/L, and has a high positive rate in early diagnosis (sensitivity of 50.3%).
CYFRA21-1 (fragment of cytokeratin 19)
Broad-spectrum TM, non-small cell lung cancer-associated antigen, with a sensitivity of 93.8% for diagnosis of squamous lung cancer. Dynamic monitoring of this indicator can be used to better observe changes in efficacy.
TRACP-5b (anti-tartrate acid phosphatase 5b)
TRACP-5b is secreted by osteoclasts, and it is elevated in the blood when osteolytic injury occurs. Therefore, plasma TRACP-5b can be used as an early warning indicator of bone metastasis in malignant tumors such as lung cancer.
sB7-H3 (soluble B7-H3)
Abnormal expression exists in tissues of lung cancer, prostate cancer, cervical cancer and gastric cancer. sB7-H3, CEA,CYFRA21-1 are detected more efficiently in lung cancer patients. sB7-H3 can be used as an early warning indicator of bone metastasis in malignant tumors such as lung cancer.
TuM2-PK (tumor M2-type pyruvate kinase)
Significantly elevated levels of TuM2-PK can indicate tumor progression in lung cancer patients, with a sensitivity of 71.64% for non-small cell lung cancer serum detection.

03. Hepatocellular carcinoma serum TM

AFP (alpha-fetoprotein)
The diagnostic criterion for primary liver cancer is 0-25 ng/mL. If active liver disease, germinal gland embryonal tumors, and pregnancy are not considered, a diagnosis of primary liver cancer can be made if quantitative serum measurements of AFP are more than 400 ng/mL for four weeks, or more than 200 ng/mL for eight weeks.
DCP (abnormal prothrombin)
An abnormal clotting factor that is a key factor in the malignant proliferation of hepatocytes and has a sensitivity of 77% in the early diagnosis of HCC.
GPC3 (phosphatidylinositol proteoglycan-3)
Belonging to the proteoglycan family, GPC3 has potential as a diagnostic marker for early hepatocellular carcinoma since it can be detected in hepatocellular carcinoma cells but not in benign liver tissue.
OPN (osteobridging protein)
A secreted phosphorylated glycoprotein that is highly expressed in hepatocellular carcinoma. It is also highly expressed in many other cancers such as lung, breast and colorectal cancers.
GP73 (Golgi Protein-73)
It belongs to a transmembrane protein of the Golgi apparatus, and can be detected in the serum of patients with liver diseases, especially hepatocellular carcinoma, and is not related to the cause of liver cirrhosis, liver function and tumor size.
MMP1 (matrix metalloproteinase 1)
MMP1 has good discriminatory ability for hepatocellular carcinoma with AEP level <20 ng/mL and can be a biological marker for early diagnosis of hepatocellular carcinoma.

04. Gastric cancer serum TM

CA72-4 (glycan antigen CA72-4)
The level of CA72-4 in normal human serum is < 6 U/mL, and abnormal elevation is mainly seen in human adenocarcinoma tissues. It is currently recognized as a better tumor marker for diagnosis of gastric cancer, and its specificity is better than that of CA19-9 and CEA.
MG7-AG (human gastric cancer MG7 antigen)
The concentration of MG7-AG in serum is increasing from superficial/ shallow/ erosion/ ulcer/ atrophic gastritis/ atypical hyperplasia to gastric cancer, in which the positive rate of gastric cancer is 51.61%, and the detection rate is high in early gastric cancer.
PG (Pepsinogen)
PG is a precursor of pepsin which is inactive in gastric juice. low PGⅠ, PGⅠ/PGⅡ should be taken seriously, and the level and ratio of PGⅠ, PGⅡ, PGⅡ is an important indicator for judging the effect of treatment of gastric cancer and postoperative recurrence.
CA 50 (glycan antigen 50)
In all gastric cancers, its determination level and positive rate are on the rise, lower in early and middle stages, and significantly higher in patients with advanced stages, which is related to the metastatic spread of the tumor.

05. Serum TM in ovarian cancer

In addition to common tumor markers such as CA125, CA19-9, CEA and AFP, there are also the following markers:
HCG (chorionic gonadotropin)
HCG is mainly produced by tumors during non-pregnancy. Among various tumor markers, β- HCG has higher sensitivity and specificity, and has important clinical application value in ovarian primary choriocarcinoma, embryonal carcinoma, and mixed genital cancer.
LDH (lactate dehydrogenase)
Lower overall specificity, only for epithelial and germ cell tumors.
M-CSF (macrophage colony stimulating factor)
Currently not specific and closely related to tumor progression, but clinically useful for diagnosis and follow-up treatment of ovarian cancer.
HE4 (Human Epitope Protein 4)
HE4 is highly expressed in a variety of cancers, including ovarian cancer, lung cancer, colon cancer and breast cancer, and has high specificity for ovarian cancer, which can be used as an important tool for early screening and diagnosis of ovarian cancer.

06. Breast cancer serum TM

In addition to CEA and CA15-3 mentioned above, there are the following indicators:
ER and PR (estrogen receptor and progesterone receptor)
Estrogen receptor (ER) and PR are important biological markers for the development of breast cancer. The remission rate, recurrence rate and prognosis of estrogen receptor (ER) and PR (PR)-positive breast cancer after endocrine therapy are favorable.
HER-2 (Human Epidermal Growth Factor Receptor-2)
Activation of HER-2 is more prevalent in human breast cancer and is generally expressed in cells without the hormone receptor. Our previous study found that high expression of HER-2 was closely associated with lymph node metastasis, tumor stage and prognosis, whereas it was closely associated with ER and PR, and was closely related to patient prognosis.
TPA (tissue polypeptide antigen)
TPA is an embryonic-derived protein widely distributed in cell membranes and organelles in tumor tissues, and its expression level in patients with breast cancer metastasis is as high as 86% compared to CA15-3.
CD44.
A membrane-penetrating glycoprotein located on the cell surface or in soluble form in malignant tumor tissues, considered a tumor marker that can be used to predict breast cancer metastasis.
VEGF (Vascular Endothelial Growth Factor)
Studies have shown that the expression level of VEGF is significantly elevated in breast cancer and is closely related to tumor cell invasion and metastasis; therefore, the role and mechanism of VEGF in breast cancer are still unclear.

07. Endometrial cancer TM

Among the tumor markers associated with endometrial cancer, in addition to CA125,CA19-9, ER and PR, the following are also included:
Histone methylation transferase (MMSET)
Our previous study found that the expression level of MMSET was significantly elevated in endometrial cancer and positively correlated with the degree of tumor malignancy, suggesting that MMSET may be an independent risk factor closely related to tumorigenesis and development.
Visceral adiponectin
Adiponectin is closely related to the development of many kinds of tumors, as well as endometrial cancer. The expression of adiponectin increases with the thickness of endometrial tissue and with the development of endometrial cancer.
YKL-40
Also known as human chondrocyte glycoprotein-39, it is a member of the mammalian 18-glycosyl hydrolase family, and shows high expression in a variety of malignant tumor tissues and patients’ sera, such as breast, colon, cervical, endometrial, and ovarian cancers.

08. Colorectal cancer TM

In addition to the highly sensitive CEA, glycan antigens (CA19-9, CA72-4, CA125, etc.):
lectins DC-SIGN and DC-SIGNR
are a class of specific receptors expressed on the surface of dendritic cells (DCs) with early diagnostic potential for colorectal cancer, and their expression in serum and tissues may affect the survival of colorectal cancer patients.
CHGA (human chromogranin A)
A protein secreted by neuroendocrine cells, if its level is high, it can be used for pancreatic neuroendocrine tumors, pheochromocytomas, or paragangliomas.CHGA is expressed at low levels in colorectal cancer, providing new ideas for the diagnosis of colorectal cancer.
Interleukin (IL)
Interleukin-6 can combine with CEA and CA19-9, which is helpful for the diagnosis of colorectal cancer; IL-35 is highly expressed in colorectal cancer and positively correlates with the degree of malignancy and clinical stage of colorectal cancer; the expression level of interleukin-38 positively correlates with the degree of malignancy of the tumor.

09. Prostate cancer serum TM

PSA (Prostate Cancer Specific Antigen)
Due to its unique tissue specificity, it has led to a significant increase in the detection rate of prostate cancer in the early, asymptomatic and treatable stages.
F-PSA/T-PSA Ratio
PSA consists of total PSA (T-PSA) and free PSA (F-PSA). F- PSA and T- PSA can be measured simultaneously, and a F- PSA/T- PSA <0.16 may indicate the occurrence of prostate cancer.

10. Bladder Cancer TM

BTA (Bladder Tumor Antigen)
BTA test is mainly qualitative and some reports show that its sensitivity can reach 86.9%. However, since BTA test is susceptible to interference from benign tumors in the urinary system, it is usually not considered as the first choice for bladder tumors, and is more often used as an adjunct to cystoscopy.
NMP22 (Nuclear Matrix Protein)
NMP22 is a specific nuclear matrix protein that is highly expressed in bladder cancer tissues and abundantly present in urinary transplant epithelial cells.
BLCA-4 (Bladder cancer-specific nuclear matrix protein 4)
BLCA-4 is highly expressed in tumor tissues associated with bladder cancer, but is not expressed in normal bladder urinary tract epithelium. Therefore, the detection of BLCA-4 level in urine is of great value for early screening and diagnosis of bladder tumors.
miRNA (micro RNA)
miRNAs have specific expression profiles in cancer cells and tissues and can enter the body fluid circulation. Circulating free miRNAs can be detected in serum, plasma, and other body fluids. mature miRNAs are very stable in body fluids and have a very high specificity in different cancer states. The relatively high chemical stability in fresh or formalin-fixed tissues and body fluids, compared to other RNAs, is another advantage of miRNAs that increases their potential as diagnostic markers. This allows miRNAs to serve as potential non-invasive tumor markers for human cancers.

Survivin and caspase-3 (cysteine aspartate protease)
In bladder cancer patients, high expression of survivin is associated with the development of bladder cancer. Caspase-3 is an apoptotic factor, and high expression of survivin can directly or indirectly inhibit the normal expression of caspase-3, which leads to the imbalance of normal apoptosis in the human body, and ultimately leads to the development of tumors and metastasis, so it is important to examine the levels of survivin and caspase-3 expression in bladder cancer tissues. Detection of survivin and Caspase-3 expression levels in bladder cancer tissues can be used as a means to determine the prognosis of bladder cancer patients after surgery.

11. Pituitary tumor TM

Ki-67 Antigen
Tends to be highly expressed in aggressive pituitary adenomas, and its expression correlates significantly with the growth rate of pituitary adenomas. Ki-67 expression ranges are useful in planning pituitary adenoma therapy and are recommended as a routine test.

Telomerase reverse transcriptase (TERT) promoter
Our previous study found that there are genetic variants and methylation modifications in the promoter region of the TERT gene, suggesting that methylation modifications in the promoter region of the TERT gene could be an important indicator for predicting tumor metastasis and recurrence.

MCM7 (microchromosome maintenance protein family)
The high expression of MCM7 is closely associated with the early progression and recurrence of pituitary adenomas, and MCM7, as a marker for determining the clinical prognosis of pituitary adenomas, contains more abundant and reliable information than Ki-67.

12. Melanoma TM

S100B
S100B is one of the most used markers in melanoma, especially metastatic melanoma. Plasma S100B concentration is closely related to patient prognosis, and the higher its concentration, the worse the patient’s prognosis.
MIA (Melanoma Activity Inhibitory Protein)
It is an autocrine oncogene obtained from the malignant melanoma cell line HTZ-19, which is significantly highly expressed in the malignant melanoma cell line HTZ-19 and hardly expressed in keratinized cells and other tissues.

13. Osteosarcoma TM

ALP (Alkaline phosphatase)
Alkaline phosphatase (ALP), a metalloproteinase, is useful in the diagnosis and prognosis of osteosarcoma.
Statement:
①Testing instruments are different and normal ranges vary slightly, please follow the advice or guidance of your doctor or healthcare professional.
②The information is from the Internet, only for medical science, if there is any infringement, please contact to delete.

Sudden elevation of TM should be taken into account, but it should not be used as the basis for the diagnosis of malignant tumors, and should be combined with clinical symptoms, imaging and pathology to make a comprehensive judgment, as well as continue to monitor the changes in TM.