Assessment of serum HE4 levels throughout the normal menstrual cycle

Moore, Richard G.; Plante, Beth J.; Hartnett, Erin; Mitchel, Jessica; Raker, Christina; Vitek, Wendy; Eklund, Elizabeth; Lambert‐Messerlian, Geralyn

doi:10.1016/j.ajog.2017.02.029

Cited by 7 publications

(2 citation statements)

References 20 publications

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“…While some authors observed higher HE4 concentrations in the ovulatory phase compared to that measured in the follicular and luteal phases (62), others affirmed that HE values are not dependent on menstrual cycle or hormonal treatment (63,64).…”

Section: He4mentioning

confidence: 96%

Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to future perspective

Montagnana¹,

Benati²,

Danese³

2017

Ann. Transl. Med.

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Ovarian cancer (OC) represents the most lethal gynecological cancer and the poor prognosis is often attributable to late diagnosis. The diagnostic approach to woman presenting with pelvic mass is difficult and differential diagnosis often requires invasive histological examination. Serum CA125 and HE4, as well as the most of the other serum biomarkers discovered and validated, are not sufficiently sensitive and specific to make early diagnosis. Moreover, conflicting results exist about the improvement of diagnostic performance by using multivariate index assays, developed by combining circulating biomarkers with other variables (i.e., ultrasound and/or menopausal status and/or age), in comparison to CA125 or HE4 alone. In the last years, several studies focused on the microRNAs (miRs), short single-stranded non-coding RNA that regulate several messenger RNAs (mRNAs). As in other cancer types, the aberrant miRs expression has been demonstrated in gynecological cancers, in both tissues and serum samples. In particular, the diagnostic performance of single or miRs panels resulted very high. However, to date, despite the potential clinical utility has been demonstrated, none of these miRs has been validated in large OC populations.

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Section: He4mentioning

confidence: 96%

Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to future perspective

Montagnana¹,

Benati²,

Danese³

2017

Ann. Transl. Med.

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“…HE4's ability to distinguish EOC from benign masses is superior to CA-125. But the level of HE4 is increased by multiple non-ovarian influences and various malignancies, predominantly those originating from the reproductive system but also encompassing respiratory cancers [5] [6] . Thus, the discovery of potential selective biomarker that is absent in the sera or reproductive organs of healthy female but present in ovarian cancer patients are immensely needed.…”

Section: Introductionmentioning

confidence: 99%

The prion-like protein Doppel: A soluble biomarker steering ovarian cancer’s peritoneal to circulatory dissemination

Azam,

Zhang,

Wahab

et al. 2024

Preprint

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Detecting ovarian cancer (OC) early using existing biomarkers, e.g., cancer antigen 125 (CA125), is challenging due to its ubiquitous expression in many tissues. Doppel, a prion-like protein, expresses in male reproductive organ but absent in female reproductive systems and healthy tissues, but plays an important role in neoangiogenesis. Here, we have shown two platforms, soluble Doppel in sera/ascites and Doppel expressed circulating tumor cells (Dpl+CTC) in the whole blood, to detect subsets of epithelial OC (EOC). Increased level of Doppel in the sera of OC patients, in three different cohorts, confirm Doppel as OC specific biomarker. Serum Doppel level distinguishes EOC subtypes and early stages HGSOCs from non-cancerous conditions with high sensitivity and specificity. Stratifying the EOCs based on Doppel level, we categorized them into Doppel-high (Dplhi) and Doppel-low (Dpllow) groups. Using ascites-derived organoids and single cell sequencing of whole ascites of Dplhi and Dpllow patients, we identify that Doppel induces epithelial-mesenchymal transition (EMT) and creates an immunosuppressive microenvironment, respectively. Doppel levels in the sera/ascites correlate with the changes of Dpl+CTC number in whole blood, highlighting the association of Doppel-induced EMT with CTC dissemination in circulation. Thus, Doppel-based detection of EOC subtypes could be a promising platform as clinical biomarker and link Doppel-axis with OC dissemination.

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