Published online Oct 15, 2020. doi: 10.4251/wjgo.v12.i10.1167
Peer-review started: April 13, 2020
First decision: April 26, 2020
Revised: May 24, 2020
Accepted: August 25, 2020
Article in press: August 25, 2020
Published online: October 15, 2020
Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer in East Asian countries especially in China, where it accounts for more than 90% of total EC cases. Effective screening and early diagnosis are the key for improved management of ESCC patients. Tumor markers used for diagnosis and follow-up of patients with ESCC include carcinoembryonic antigen (CEA), carbohydrate antigen 72-4 (CA72-4), CA19-9, alpha fetal protein (AFP), CA24-2, and squamous cell carcinoma antigen. However, clinical use of these markers for diagnosis of ESCC has been restricted because of the lack of sensitivity.
The early diagnosis of ESCC remains a clinical challenge. Biomarkers predictive of early diagnosis and prognosis may help design more effective and even targeted therapies for ESCC patients. To date, overexpression of human epididymis protein 4 (HE4) has been demonstrated in a range of malignant neoplasms. The sensitivity and specificity of HE4 serum expression in epithelial ovarian cancer patients are superior to those of other serum biomarkers, which led to the United States Food and Drug Administration approval of HE4 as a biomarker for the detection of ovarian cancer in women presenting with an ovarian cyst or pelvic mass as part of the risk of ovarian malignancy algorithm. However, the diagnostic value of serum HE4 in ESCC patients remains unknown.
We have carried out this study to investigate the diagnostic value of HE4 in patients with ESCC. The relationship between clinical, demographic, and pathological characteristics and HE4 was also assessed.
Eighty patients diagnosed with ESCC who underwent surgical resection at our hospital between January 2017 and June 2019 were included in this study. They were compared to a control group of 56 patients with benign esophageal disease. Serum levels of HE4, CEA, AFP, and CA19-9 were detected using ELISA.
We found that serum HE4 level was higher in cases with ESCC than in the controls. Serum HE4 levels had a sensitivity of 66.2% and specificity of 78.6% when the cut-off value was set at 3.9 ng/mL. Moreover, the combined HE4 and CA19-9 increased the sensitivity to 83.33%, and interestingly, the combination of HE4 with CEA led to the most powerful sensitivity of 87.5%. Furthermore, a positive correlation was observed between HE4 serum levels and pathological T and N stages, but there was no correlation between HE4 serum levels and ESCC patients' gender and tumor location.
HE4 is significantly higher expressed in patients with ESCC, and the staining intensity is inversely correlated with the pathological stage. The results of this study suggest that detection of serum HE4 levels may be useful in auxiliary diagnosis and evaluation of the progression of ESCC.
Biomarkers predictive of patient prognosis may help design more effective and targeted therapies for ESCC. This study indicates that ESCC patients have abnormal expression of serum tumor markers such as HE4, which therefore may be useful for auxiliary diagnosis and evaluation of ESCC. Furthermore, it seems that detection of serum HE4 levels may potentially be useful in auxiliary early diagnosis and evaluation of the progression of ESCC patients. However, further studies are required to verify ESCC progression according to the serum HE4 level at the time of diagnosis, and even treatment can be planned accordingly.