Tumor markers CA125 and HE4: “double insurance” for ovarian cancer patients?

Author: Cui Liyan, Chief Physician, Peking University Third Hospital

Reviewer: Duan Hua, Chief Physician, Beijing Obstetrics and Gynecology Hospital, Capital Medical University

Ovarian cancer, as one of the malignant tumors in the female reproductive system, is often difficult to detect in the early stages due to its nonspecific symptoms, thus affecting the best time for treatment. However, with the advancement of medical technology, the detection of tumor markers to assist in the diagnosis of ovarian cancer has become an important clinical method. The following will introduce in detail the tumor markers related to ovarian cancer, especially CA125 and HE4, and explore their application in the diagnosis, treatment, monitoring and prognosis evaluation of ovarian cancer.

Symptoms of ovarian cancer include abdominal distension, abdominal pain, abdominal mass, fever, weight loss, etc., but these symptoms may also occur in other diseases, so they are not specific. When women experience these symptoms, they should be alert to the possibility of ovarian cancer and seek medical attention in time. Clinically, the diagnosis of ovarian cancer mainly relies on imaging examinations and pathological examinations, while the detection of tumor markers is gradually gaining attention as a non-invasive auxiliary method.

Tumor markers are substances related to tumors that are synthesized or released by tumor cells during tumor occurrence and proliferation, or produced by the body in response to tumor cells. They can be detected in blood, tissues or body fluids. There are many tumor markers related to ovarian cancer, of which CA125 and HE4 are the most common.

CA125, or cancer antigen 125, is a high-molecular glycoprotein that is closely related to the onset of ovarian cancer. Under normal physiological conditions, CA125 can be expressed in the coelomic epithelium and amnion during embryonic development. In general adult women, the level of CA125 is low. However, in patients with ovarian cancer, the level of CA125 is usually significantly increased. It should be noted that an increase in CA125 does not necessarily mean ovarian cancer, but may also be associated with benign diseases such as benign ovarian lesions, adenomyosis, endometriosis, ovarian chocolate cysts, and inflammation of other glands. In addition, the level of CA125 may also be affected by the detection system, laboratory variation, and biological variation. Therefore, in clinical practice, the increase in CA125 levels exceeding twice the upper limit of the normal reference range is usually used as the standard for judging whether it is truly elevated. Despite this, we still cannot simply determine whether we have a tumor through a single CA125 level test, but need to combine medical history, imaging examinations, and pathological examinations to make a comprehensive judgment.

Figure 1 Original copyright image, no permission to reprint

HE4, or human epididymis protein 4, is a newly discovered ovarian cancer-related tumor marker in the past decade. Compared with CA125, HE4 has a higher specificity in ovarian cancer, so it has also attracted much attention. HE4 can be expressed not only in ovarian tissue, but also in other tissues such as the respiratory system. However, studies on ovarian cancer have found that the increase in HE4 in ovarian cancer patients is more obvious. In normal adults, the level of HE4 is usually lower than 140pmol/L. When the level of HE4 increases, it is also necessary to be alert to the possibility of ovarian cancer, but the possibility of other benign diseases also needs to be considered. Similar to CA125, the increase in HE4 cannot be used as the only basis for the diagnosis of ovarian cancer, but needs to be combined with other examination methods for comprehensive judgment.

In addition to CA125 and HE4, there are some other ovarian cancer-related tumor markers, such as CA19-9, AFP, CEA, CA724, etc. Although these markers are not as common as CA125 and HE4, they also have certain value in the diagnosis and monitoring of ovarian cancer. In the initial screening, in order to exclude the possibility of ovarian cancer as much as possible, it is usually recommended to test multiple tumor markers at the same time. However, in patients who have been diagnosed with ovarian cancer in the later stage, in order to judge the efficacy and monitor recurrence, some elevated markers can be selected for regular monitoring.

Tumor marker testing is a non-invasive test performed by drawing blood. When elevated tumor marker levels are found, clinicians usually make a comprehensive judgment based on the patient's medical history, imaging examinations, and pathological examinations. For ovarian cancer, pathological testing remains the gold standard for diagnosis. However, tumor marker testing still has important value in early screening, efficacy assessment, and recurrence monitoring of ovarian cancer.

Figure 2 Original copyright image, no permission to reprint

It is worth noting that the level of tumor markers can not only be used to assist in the diagnosis of ovarian cancer, but also to assess the patient's prognosis. Studies have shown that patients with low HE4 levels have a higher survival rate, while patients with high HE4 levels have a lower survival rate. Taking 500pmol/L as the standard, the five-year survival rate of patients below this level is about 59%, while the five-year survival rate of patients above this level is only 27%. This result suggests that by monitoring the level of HE4, we can predict the patient's prognosis to a certain extent, thereby providing a more personalized decision-making basis for clinical treatment.