What Is the CA-125 Marker?

CA-125 (cancer antigen 125, cancer antigen 125, or carbohydrate antigen 125), also known as mucin 16 or MUC16, is a protein that is encoded by the MUC16 gene in humans. MUC16 is a member of the glycoproteins of the mucin family. CA-125 has found applications as tumor markers or biomarkers that can be elevated in certain types of blood in certain cancer patients, or benign other conditions ^[1] .

Carbohydrate antigen 125 (Carbohydrate antigen 125) is derived from epithelial cells of the body cavity and can be expressed in normal tissues.

CA-125 was initially detected using a murine monoclonal antibody named OC125. Robert Bast, Robert Knapp, and his team isolated this monoclonal antibody for the first time in 1981. The protein was named "cancer antigen 125" because OC125 is the 125th antibody raised against the ovarian cancer cell line under study ^[2]

CA125 is a membrane-associated mucin, which has a single transmembrane domain. The unique property of CA125 is its large size. CA125 is more than double MUC1 and MUC4 and contains about 22,000 amino acids, making it the largest membrane-associated mucin.

CA125 consists of three different domains:

One N-terminal domain tandem repeat domain One C-terminal domain

Both the N-terminal and tandem repeat domains are fully extracellular and highly O-glycosylated. All mucins contain a tandem repeat domain with repeating amino acid sequences that are high in serine, threonine, and proline. The C-terminal domain contains multiple cellular SEA (sea urchin sperm protein, enterokinase, and agrin) modules, a transmembrane domain, and a cytoplasmic tail. The extracellular domain of CA125 can be released from the cell surface by proteolytic cleavage. CA125 is thought to be cleaved from one site in the SEA module.

CA125 is a component of the ocular surface (including the cornea and conjunctiva), the respiratory tract and the female reproductive tract epithelium. Because CA125 is highly glycosylated, it creates a hydrophilic environment that acts as a lubricant barrier for foreign particles and infectious agents on the epithelial apical membrane. In addition, the cytoplasmic tail of CA125 has been shown to interact with the cytoskeleton by binding to members of the ERM protein family. Mucin 16 expression has been shown to change in dry eye, cystic fibrosis, and several types of cancer. ^[1]

CA-125 is the most commonly used biomarker for ovarian cancer detection. Medical associations, including the American Congress of Obstetricians and Gynecologists, recommend routine CA-125 screening or other screening for women with an average risk of ovarian cancer. Reasons for this include evidence that fuzzing test results are more likely to lead to further invasive, harmful, and unnecessary health care than ovarian cancer that may be detected in women with an average of ovarian cancer.

Approximately 90% of women with advanced ovarian cancer have elevated CA-125 levels in their serum, making CA-125 a useful tool for detecting ovarian cancer after symptoms appear. Monitoring CA-125 serum levels can also be used to determine ovarian cancer response to treatment (the disease-free survival time is related to the rate of decline of CA-125) and to predict the prognosis of patients after treatment. This is because the persistence of high levels of CA-125 during treatment is associated with lower survival rates for patients. In addition, an increase in CA-125 levels in individuals during remission is a strong predictor of ovarian cancer recurrence. In fact, the increase in CA-125 levels may precede clinical evidence of disease recurrence at intervals of 3 to 6 months.

The prognosis involves initial and post-treatment CA-125 values. Preoperative values> 65 U / mL indicate a poor prognosis. A persistent increase after chemotherapy indicates a poor prognosis. The half-life of CA-125 after chemotherapy is associated with prognosis (increased survival of patients with CA-125 half-life <20 days). Normalized time (decline rate of CA-125) affects prognosis, and faster normalization within 3 cycles of chemotherapy is associated with improved survival.

In April 2011, the National Institute of Health and Clinical Excellence (NICE) recommended that CA-125 blood tests should be offered to women with ovarian cancer symptoms. The purpose of this guide is to help diagnose the disease at an early stage where treatment is more likely to succeed. Women with higher levels of markers in the blood will then undergo an ultrasound scan to determine if further testing is needed.

In one case, elevated CA-125 serum levels were observed in male patients with IgE myeloma, however more cases are needed to determine the clinical significance of CA-125 in myeloma.

MUC16 (CA-125) has been shown to play a role in promoting tumorigenesis and tumor proliferation through several different mechanisms.

Carbohydrate antigen CA125 immune system escapes

One way MUC16 helps tumors grow is by suppressing the natural killer cell response, thereby protecting cancer cells from the immune response. Further evidence that MUC16 can protect tumor cells from the immune system suggests that the highly glycosylated tandem repeat domain of MUC16 can bind to galectin-1, an immunosuppressive protein.

Carbohydrate antigen CA125 metastasis invasion

MUC16 is also thought to be involved in intercellular interactions that enable tumor cells to metastasize. This evidence suggests that MUC16 selectively binds to mesothelin, a glycoprotein commonly expressed by peritoneal mesothelial cells (the inner wall of the abdominal cavity). The interaction between MUC16 and mesothelin is considered to be the first step for tumor cells to invade the peritoneum. Region (residues 296-359), which consists of 64 amino acids at the N-terminus of mesothelin on the cell surface, has been experimentally established as a functional binding domain (named IAB) of MUC16 / CA125. An immunoadhesin consisting of the IAB domain of human mesothelin and the human Fc portion has the ability to disrupt the adhesion of heterotypic cancer cells mediated by MUC16-mesothelin interaction.

Mesothelin has also been found to be expressed in several types of cancer, including mesothelioma, ovarian cancer, and squamous cell carcinoma. Since corticosteroids are also produced by tumor cells, the interaction between MUC16 expression and mesothelium may be helpful in the accumulation of other tumor cells to the metastatic site, thereby increasing the size of metastases.

Carbohydrate antigen CA125 induces exercise

Evidence suggests that expression of the cytoplasmic tail of MUC16 causes tumor cells to grow, promotes cell movement and may promote invasion. This appears to be due to the ability of the C-terminal domain of MUC16 to promote signaling that results in reduced expression of E-cadherin and increased expression of N-cadherin and vimentin, which is consistent with epithelial cell expression mode. Mesenchymal cell transformation.

Carbohydrate antigen CA125 chemotherapy resistance

MUC16 may also play a role in reducing the sensitivity of cancer cells to drug treatment. For example, MUC16 overexpression has been shown to protect cells from genotoxic drugs such as cisplatin. ^[3]