Clinical Applications of the Human Epididymis Protein 4 (HE4) Program

Human epididymis protein 4 (HE4) belongs to the family of whey acidic 4-disulfide bond core proteins and was originally thought to be a protease inhibitor associated with sperm maturation. Immunohistochemical and gene microarray studies have confirmed that it is barely expressed in human normal ovarian tissues; in malignant tissues, it is commonly upregulated in ovarian cancer and is one of the most commonly upregulated genes expressed in ovarian cancer; and is not expressed or is lowly expressed in most non-ovarian cancers. In contrast, RT-PCR studies revealed that HE4 was highly expressed in ovarian cancer cell lines, and cell cultures contained the secreted form of HE4.

In a comparative study of ovarian cancer patients with a healthy status, Hellstrom et al. found that HE4 had a specificity of 95% and a sensitivity of 67% for detecting ovarian cancer. The specificity was significantly higher than that of CA125 alone. Combined with carcinoma antigen 125, the test was more accurate in predicting ovarian cancer, with a sensitivity and specificity of 76% and 95%, respectively.

1. Human epididymis protein 4 (HE4) has an important diagnostic value in identifying pelvic masses, benign and malignant tumors

Among the existing tumor markers list, HE4 as a single tumor marker has the most sensitive performance in detecting ovarian cancer, with higher sensitivity than CA125. In addition, HE4 has good sensitivity in patients with stageⅠ, Ⅱand Ⅲ ovarian cancer. 93% of ovarian cancer patients overexpressed HE4 in plasma. The diagnostic sensitivity and specificity of HE4 in the serum of ovarian cancer patients were 82.5% and 95%, respectively. Click here for the information about ca19 9 cancer markerca153 cancer marker, ca 72-4 tumor marker, etc.

In benign pelvic masses, there was an 8% elevation in HE4 levels compared with a 29% elevation in CA125. In identifying pelvic masses and benign and malignant tumors, HE4 showed a non-normal distribution in patients with ovarian cancer and varied significantly in ovarian-related benign and malignant tumors, with statistically significant differences in premenopause and postmenopause. Meanwhile, the level of human epididymis protein 4 (HE4) increased as the stage of ovarian cancer progression increased in patients.

2. Human epididymis protein 4 (HE4) is better than CA125 for prognosis and postoperative monitoring of ovarian cancer

The concentration level of HE4 protein can reflect the development trend of the disease and is used to monitor the effect of surgery and chemotherapy in ovarian cancer patients. The HE4 level can be measured 1 week after surgery. If the treatment is effective and the HE4 level decreases significantly, the situation can be judged to be in remission and stable; if the treatment is ineffective and the HE4 level does not change significantly or shows an increase, the treatment plan should be changed promptly.

Compared with CA125 for judging the efficacy of treatment, human epididymis protein 4 (HE4) changes more and is more effective for judging the prognosis of ovarian cancer patients. Regarding the frequency of HE4 testing, it should be performed once every 3 months within 1 year after surgery, then 2 times a year for 2 to 3 years after surgery, and once a year is recommended for more than 3 years after surgery.

If the test reveals a slight increase in HE4 level, it suggests that there may be signs of recurrence. Patients are advised to undergo imaging examinations to confirm the recurrence for timely treatment and enhance the clinical diagnosis and treatment.

3. Combined testing of human epididymis protein 4 (HE4) and CA125 and the risk of ROMA

When combined testing of HE4 and CA125 levels is combined with patients' menstrual status (premenopausal or postmenopausal), the corresponding mathematical model - Risk of Ovarian Malignancy (ROMA) model was established by regression analysis to predict the risk of pelvic masses as ovarian cancer, and this formula can calculate the ovarian cancer risk prediction index for premenopausal and postmenopausal women respectively. The ROMA model was used to classify patients with clinical pelvic masses as being at high risk of developing ovarian cancer.

It provides a new means for early diagnosis and improved prognosis for low-risk groups and ovarian cancer.