Definition

 

Carbohydrate antigen (CA) 19-9 is an antigen released by pancreatic cancer cells. It can also be called a tumor marker. CA 19-9, also known as sialic acid lewis-a (sLea), is expressed on the surface of cancer cells in the form of glycolipids and O-linked glycoproteins. It is a glycoprotein that is distributed in the pancreas, liver, gallbladder and intestines of the fetus during the embryonic stage. Adults also have a small number of pancreas, gallbladder and other parts, and the normal CA19-9 value is not higher than 37U/ml. In pancreatic cancer, hepatobiliary and gastrointestinal tumors, the level of CA19-9 in the blood can be significantly increased, especially pancreatic cancer, Its sensitivity and specificity is as high as 90%, which has important value for disease progression, surgical efficacy, prognosis evaluation and recurrence diagnosis. CA19-9 has high sensitivity but low specificity. CA19-9 is widely present in normal glandular epithelial cells and tissues with secretory function and is therefore not a tumor-specific antigen. CA19-9 can also be detected in most normal human serum.

 

 

Fig. 1 Chemical structure of Sialyl Lewis a

Function

 

Tumor markers refer to a class of substances that are synthesized and secreted by the gene expression of tumor cells or abnormally produced and/or elevated by the body's response to tumor cells during the occurrence and proliferation of malignant tumors, including proteins, hormones, sugar chain antigens, enzymes (isoenzymes), polyamines, and oncogene products, etc., which exist in the patient's blood, body fluids, cells or tissues. CA19-9 is used in the diagnosis of pancreatic cancer, but it is also a marker of pancreatic tissue damage that might be caused by diabetes. Serum CA 19-9 is currently the most widely validated biomarker for pancreatic cancer and has a variety of clinical applications. The sensitivity of serum CA 19-9 level for diagnosing pancreatic cancer in symptomatic patients is 79% ~ 81%, and the specificity is 82% ~ 90%. Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels (<37 U/mL) have a prolonged median survival (32-36 months) compared to patients with elevated levels (>37 U/mL) (12-15 months). A CA 19-9 serum level of <100 U/mL implies likely resectable disease whereas levels >100 U/mL suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase.

 

 

Fig. 2 Structure and biosynthesis of Lewis Antigens. Monosaccharides are depicted. Blue square: N-acetylglucosamine

(GlcNAc); yellow square: N-acetylgalactosamine (GalNAc); yellow circle: galactose (Gal); red triangle: fucose (Fuc); pink

diamond: sialic acid (Sia). Anomers, linkage positions, and enzymes involved in the reactions are indicated.

 

 

Fig. 3 Proposed model of the elevation of circulating CA19.9 in pancreatic cancer patients.

 

Clinical Application

 

CA19-9 and Pancreatic Cancer

 

CA19-9 is by far the highest sensitivity marker for pancreatic cancer.CA19-9 was the most effective marker for the diagnosis of pancreatic cancer. The sensitivity of CA19-9 in the diagnosis of TNM stage I of pancreatic cancer was 60.7%, and that of TNM stage 11 was 78.4%.

-- Judging the difficulty of surgery: CA19-9 level is related to the development stage of pancreatic cancer, and the content in serum can indicate the difficulty of surgery;

-- Suggestive prognosis: preoperative CA19-9 level has a certain prognostic effect, low prognosis is good, 37Ku/L can be used as a preliminary value to distinguish the survival of patients, postoperative CA19-9 level to normal survival is longer than not decreasing;

-- Monitoring for tumor recurrence: CA19-9 may be elevated before radiographic diagnosis when tumor recurrence occurs.

 

CA19-9 and Other Diseases

 

The clinical sensitivity for gastric cancer was 26-60%. The sensitivity for epithelial ovarian carcinoma was 36~42%, while that for mucinous ovarian carcinoma was 76~83%. It is an ideal index for the diagnosis of mucinous ovarian carcinoma.

-- Gastric cancer: CA72-4 and CEA can be measured simultaneously to improve diagnostic sensitivity and specificity;

-- Endometrial cancer: CA125 can be combined to improve sensitivity;

-- Benign and inflammatory lesions of the digestive system, such as pancreatitis, mild cholestasis, and jaundice, tend to be transiently elevated and often less than 120 ku/L in concentrations below.

 

Benign diseases are the main causes of elevated CA19-9 levels, and some studies have found that benign hepatobiliary diseases can cause elevated CA19-9 levels. Elevated CA19-9 is also more common in female reproductive system diseases, such as endometriosis, ovarian cysts, teratoma, uterine fibroids, ovarian dermoid cysts, ovarian mucocele and so on. Diabetes, hyperthyroidism, thyroid nodular hyperplasia, thyroiditis and other endocrine diseases can also show elevated CA19-9. Because CA19-9 is cleared primarily from the liver, hepatobiliary disease often results in false positives, especially in the presence of jaundice. Elevated CA19-9 is also more common in female reproductive system diseases, such as endometriosis, ovarian cysts, teratoma, uterine fibroids, ovarian dermoid cysts, ovarian mucocele and so on. Diabetes, hyperthyroidism, thyroid nodular hyperplasia, thyroiditis and other endocrine diseases can also show elevated CA19-9.

Alpha Lifetech Inc. is dedicated to developing CA19-9 diagnostic regents. Alpha Lifetech Inc. is a reputable supplier focusing on research, manufacture and sales of In Vitro Diagnostic (IVD) regents. All the IVD regents offered by Alpha Lifetech Inc. have undergone strict QC validation and are certified by the COA (certificate of analysis). Meanwhile, we can provide customized services according to customers' requirements. Alpha Lifetech Inc. is committed to supply high-quality, high-sensitivity antigen and antibody products for scientific research and industrial customers. In addition to regular small packages, Alpha Lifetech Inc.'s large-scale fermentation platform also allows us to provide raw material-grade IVD regents for the majority of industrial clients.

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