Diagnostic value of urinary-to-serum human epididymis protein 4 ratio in ovarian cancer

Abstract

Abstract. Human epididymis protein 4 (HE4) is one of the best-known tumor markers for ovarian cancer (OC). Emerging evidence indicates that the evaluation of serum HE4 (S-HE4) levels may be problematic when patients have chronic kidney disease (CKD). Assaying urine for HE4 levels is non-invasive alternative for the diagnosis of OC. However, whether the combined detection of S-and urinary HE4 (U-HE4) levels distinguishes OC from CKD remains unknown. To investigate this issue, the present study recruited 31 female patients with OC, 38 female patients with CKD, and 36 healthy control (HC) females. Serum and urine samples were preoperatively collected for HE4 level detection. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance of S-HE4 level, U-HE4 level and the ratio of urinary-to-serum HE4 level (R-HE4). Data from the current study indicated that serum HE4 levels in the OC and CKD groups were significantly higher than that in the HC group. The U-HE4 level in the OC group was significantly higher than that in the CKD and HC groups. The highest R-HE4 was observed in the HC group, followed by the OC group, and the lowest R-HE4 was observed in the CKD group. ROC analysis demonstrated that the R-HE4 was useful in differentiating OC from CKD and HC. Based on the diagnostic interval of optimal cut-off values from 36.85 to 96.15, the sensitivity and specificity of R-HE4 in differentiating OC patients from non-OC patients were 82.6 and 85.4%, respectively. Thus, the combined detection of S-and U-HE4 levels facilitates the diagnosis of OC, and R-HE4 is an effective marker for differentiating OC from CKD.

Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods

“…Twelve studies explored the diagnostic and predictive potential of proteins and metabolites in urine for OC 64‐75 . Four studies show the potential of DNA methylation profiles, miRNA expression and exosomes in urine for detection 76‐79 .…”

“…Twelve studies explored the diagnostic and predictive potential of proteins and metabolites in urine for OC. [64][65][66][67][68][69][70][71][72][73][74][75] Four studies show the potential of DNA methylation profiles, miRNA expression and exosomes in urine for detection. [76][77][78][79] Although all these studies showed good performance, almost none specified which urine fraction or preservation method, if any, they used.…”

The Diagnostic Accuracy of Serum and Urine Human Epididymis Protein 4 (HE4) in Ovarian Cancer in 15,394 Subjects: An Updated Meta-Analysis

“…Details of the included studies on urine HE4 are provided in Table 2 [57][58][59][60][61]. The total number of participants involved in these five studies was 649.…”

An SPRi Biosensor for Determination of the Ovarian Cancer Marker HE4 in Human Plasma

“…The marker may be present in several isoforms with different molecular weights [1,3]; therefore, its concentration is usually expressed in pM (picomole/L). Serous HE4 concentration is strongly elevated in the case of ovarian cancer, although a certain elevation is also observed in cervical and breast cancers [4], as well as in chronic kidney disease [5]. Moreover, marker concentration strongly depends on the stage of ovarian cancer.…”

“…HE4 exhibits good selectivity and specificity (with an ROC (receiver operating characteristic) curve with an area under the curve (AUC) value of 0.91) and strongly reacts to the disease stage [4]. It should be noted that urine HE4 concentration is much higher than the serous marker concentration, and it is significantly elevated in the case of ovarian cancer [5]. The designed biosensor appears to be suitable for the determination of HE4 in both healthy individuals and ovarian cancer patients.…”