Making new biomarkers a reality: the case of serum human epididymis protein 4

Abstract

Background Measurement of human epididymis protein 4 (HE4) in serum has recently been proposed for clinical use in the framework of ovarian cancer (OvCa). We sought to retrace the translational phase and the clinical implementation steps boosting HE4’s clinical value and discuss the effects of its introduction on the diagnostic and management pathways. Methods Meta-analyses of running evidence have preliminarily suggested that HE4 may overcome carbohydrate antigen 125 (CA125) in identifying OvCa, showing however several gaps that need to be considered, i.e. definition of biomarker diagnostic performance in the early detection of OvCa, added diagnostic value, biological and lifestyle factors of variation, and optimal interpretative criteria. Investigation of the influencing factors has shown that renal impairment represents a major limitation for HE4’s diagnostic power. On the other hand, the demonstration of the substantial equivalence of results obtained by commercially available assays allows recommending harmonized thresholds for diagnostic purpose, even if the study of HE4’s biological variation has clarified that the longitudinal interpretation of the biomarker changes according to the reference change value could be more appropriate. Summary We used HE4 as an example for describing the long and bumpy road for making a new biomarker a reality, and the issues that should be checked and the information that should be provided in moving a novel biomarker from its discovery to an effective clinical adoption.

Human Epididymis Protein 4 expression in the renal cortex tissue is an independent prognostic factor in patients with renal cell carcinoma

“…For HE4 staining of TMAs, of the 26 clear cell RCC patients, only one (3.8%) was weakly positive and all others were negative for HE4 staining, although the percentage of strongly positive staining was very high for serous ovarian cancer, endometrial cancer and lung adenocarcinoma (81%, 49% and 33%, respectively.) in which cancers HE4 expression in tumor was reported as cancer biomarker [8][9][10][11][12]. Even in our study, the expression rate of HE4 in tumor tissue was very low in clear cell RCC (9.5%).…”

Diagnostic accuracy of human epididymis secretory protein 4 for lung cancer: a systematic review and meta-analysis

“…Diagnostic accuracy of human epididymis secretory protein 4 for lung cancer: a systematic review and meta-analysis Human epididymis secretory protein 4 (HE4) has been regarded as a tumor marker for ovarian cancer for a long time (9,10). Interestingly, several studies have revealed that it is also a useful diagnostic marker for lung cancer (11)(12)(13), but the results of these studies are heterogeneous.…”

HE4 in the evaluation of tumor load and prognostic stratification of high grade serous ovarian carcinoma

“…The disease dissemination score showed prognostic value in a previous study [24]. Patients were divided into a low tumor load group (dissemination score 0-12) and a high tumor load group (dissemination score [13][14][15][16][17][18][19][20][21]. In all patients treated with NACT, the disease dissemination score was calculated at diagnostic laparoscopy, before the initiation of chemotherapy.…”

“…The shortcomings of CA125 and the insidious nature of HGSC have sprouted comprehensive research on more satisfactory biomarkers in the diagnosis, treatment monitoring, and follow up of the disease [12]. Human epididymis protein 4 (HE4) was first described by Kirchhoff et al [13], and it has since been proposed as a complement to CA125 in the diagnosis of HGSC [14].…”