CA125 antigen

CA125 is a macromolecular polysaccharide protein that mainly exists in the pericardium, peritoneum, pleura and other tissues derived from fetal body cavity epithelium. It can also be expressed in normal female fallopian tubes, endometrium and cervical epithelial cells. CA125 mainly for the detection of ovarian cancer, the positive rate for epithelial ovarian cancer is relatively high. Elevated levels are also seen in cervical cancer, endometrial cancer, fallopian tube cancer, etc. Other non-gynecological malignancies such as pancreatic cancer, gastric cancer, lung cancer, breast cancer, colon cancer, etc. may also have elevated serum CA125. The carbohydrate antigen CA125 is a large glycoprotein produced by epithelial cells in certain areas of the body, including the wall layers of body cavities (such as the pericardium, pleura and peritoneum) and organs of Müllerian origin (such as the fallopian tubes, endometrium and endocervix). The molecular weight of this glycoprotein is quite large, ranging from 200,000 to 1 million. It has a circular structure and contains about 24% carbohydrate moieties. It is a high molecular weight glycoprotein complex similar to mucin and is related to immunoglobulin G (IgG). CA125 is normally synthesised and stored intracellularly. Studies have found that due to the obstruction of tight junctions and basement membranes between cells, CA125 is usually unable to enter the blood, so the concentration of CA125 in the serum of healthy people is extremely low, usually less than 35 U/mL. However, when malignant changes occur in tissues, CA125 accumulates in cells and moves to the edge of cells, which causes changes in the cell membrane, allowing the CA125 antigen to be released outside the cells. Therefore, after infiltrating tumor cells destroy the structure and cell connections of normal tissues, CA125 can enter the blood. These phenomena make CA125 a potential tumor marker.

Figure 1. Illustration of MUC16(CA125) structure and its role in ovarian cancer. (Sources: Charkhchi P, et al. 2020)

CA125 is currently the most commonly used biomarker for diagnosing epithelial ovarian cancer (EOC), and it has even been approved by the U.S. Food and Drug Administration (FDA) to monitor the effectiveness of treatment in patients with EOC. Despite this, doctors sometimes use CA125 outside of its original indications when evaluating adnexal masses. This indicator can be used alone or in combination with other serum biomarkers, pelvic ultrasound, or imaging studies to increase the clinical suspicion of malignancy of adnexal masses. There are currently multiple CA125 tests on the market, and although their detection results vary, in actual clinical applications, they are generally considered to be similar in performance. Among the many tests, CA125 (reacts with OC125) and CA125 II (combines OC125 and M11) are the most commonly used. Although CA125 II may have higher specificity, there is currently insufficient data to prove which test method is superior, and both tests are widely accepted. In the exploration of early diagnosis of ovarian cancer, CA125 protein as an indicator seems to be somewhat powerless in practical application. Especially in the early stages of the disease, its performance is not very ideal. At the same time, its specificity is also not satisfactory, especially when facing premenopausal women. As a marker for auxiliary diagnosis of ovarian epithelial cancer (EOC), it has become the focus of concentrated research by scientific researchers. So far, scientists have not found a biomarker that can accurately identify various subtypes of EOC - whether it is ovarian, fallopian tube or peritoneal subtypes; at the same time, no serum biomarker can show high sensitivity and specificity in diagnosing EOC.

The clinical significance of CA125 detection is mainly reflected in the diagnosis of ovarian cancer and other malignant tumours. CA125 is mainly used in the diagnosis and monitoring of ovarian cancer. The most commonly used tumour marker for ovarian cancer is carbohydrate antigen 125 (CA125), but its sensitivity is low in the early stages. Human epididymal protein 4 (HE4) is relatively well recognised as a new diagnostic indicator for ovarian cancer. The combined detection of HE4 and CA125 is currently the best combination for the adjunctive diagnosis of ovarian cancer. CA125 is found in the epithelial cells of the ovaries, fallopian tubes, endometrium and cervix. It is a good tumour marker for epithelial ovarian cancer and endometrial cancer and can be used to differentiate between benign and malignant ovarian masses. Dynamic monitoring of its levels is useful for prognostic analysis and treatment monitoring in ovarian cancer. The serum CA125 level in ovarian cancer is significantly elevated, but the early positive rate is low (50%~60%). The CA125 expression positivity rate in patients with ovarian serous adenocarcinoma is 82%, and the positive rate in stage III~IV lesions can reach 100%. CA125 does not increase in mucinous ovarian cancer. CA125 elevation may precede the onset of clinical symptoms, so it is a good indicator for observing the efficacy. When surgery, chemotherapy and immunotherapy are effective in patients with CA125-positive ovarian cancer, the CA125 concentration can gradually drop to the normal level after 1 week. If it cannot recover, it indicates that the treatment is ineffective or there is residual tumor. In the event of recurrence, CA125 elevation may precede the onset of clinical symptoms. CA125 elevation can also be seen in breast cancer, gastrointestinal cancer and other malignant tumors, with a positive rate of 40% for breast cancer, 50% for pancreatic cancer, 47% for gastric cancer, 41.1% for lung cancer, 34.2% for colorectal cancer, and 43% for other gynecological tumors. In addition, there are many benign gynecological diseases, such as ovarian cysts, endometriosis, cervicitis and uterine fibroids, may also elevate CA125. In the first three months of non-tumor pregnancy, pregnant women may have elevated CA125. CA125 elevation in the short term may also be related to the menstrual cycle. There are more high values 10 days before menstruation, and the average value in the proliferation period is also higher than that in the secretory period.

Cancer Antigen 125
Carbohydrate Antigen 125
Mucin 16
CA-125
OC125