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HE4

Basics

Aliases:
This biomarker is also known as:
  • WFDC2,
  • WAP four-disulfide core domain 2,
  • Major epididymis-specific protein E4,
  • WAP domain containing protein HE4-V4,
  • epididymal protein 4,
  • WAP four-disulfide core domain 2 [Precursor],
  • EDDM4,
  • WAP5,
  • dJ461P17.6,
  • epididymis-specific, whey-acidic protein type, four-disulfide core,
  • Epididymal secretory protein E4,
  • Putative protease inhibitor WAP5,

Description…

11 kDa protein that is a precursor to the epididymal secretory protein HE4; an inhibitor of an as yet unidentified protease. Highly expressed in a number of tumors cells lines, such ovarian, colon, breast, lung and renal cells lines.

Attributes

QA State: Accepted
Type: Protein
Short Name:
HGNC Name: WFDC2

Organs

The following organs have data associated with this biomarker…

Lung

Attributes

Phase: Two
QA State: Under Review

Overview

Performance Comment

Supporting Study Data

The following studies/protocols provide evidence supporting HE4 indications for the Lung…

No supporting studies or protocols found.

Organ-Specific Protocols

No organ-specific protocols defined.

Organ-Specific Publications

No organ-specific publications defined.

Organ-Specific Resources

No organ-specific resources defined.

Ovary

Attributes

Phase: Three
QA State: Accepted

Overview

Selected for study because of upregulation (mRNA) and overexpression (protein) studies in ovarian cancer.

Performance Comment

Of the 28 ovarian cancer biomarkers tested in prediagnostic specimens, from the PLCO, CA125 remains the the single best biomarker for ovarian cancer and has its strongest signal within six months of diagnosis. HE4 alone was not a strong predictor. In 2009 HE4 was FDA approved to monitor for ovarian cancer recurrence, but not for early detection.

Supporting Study Data

The following studies/protocols provide evidence supporting HE4 indications for the Ovary…

PLCO Ovarian Phase III Validation Study

Our preliminary data indicate that the performance of CA 125 as a screening test for ovarian cancer can be improved upon by additional biomarkers. With completion of one additional validation step, we will be ready to test the performance of a consensus marker panel in a phase III validation study. Given the original aims of the PLCO trial, we believe that the PLCO represents an ideal longitudinal cohort offering specimens for phase III validation of ovarian cancer biomarkers.

View more about this study
Biomarker Characteristics Summary
Notes Sensitivity Specificity Prevalence NPV PPV Specific Assay Type
Cases chosen with diagnosis of ovarian cancer (on average) 9 months prior. Controls were matched to cases by age and timing of specimen collection including general population controls (50%), false positive CA125 (25%), and family history of breast cancer (25%). All cases (n=60). 42.0 95.0 N/A N/A N/A
Cases diagnosed <= 6 months after draw (n=25). 68.0 95.0 N/A N/A N/A
Cases diagnosed > 6 months after draw (n=35). 23.0 95.0 N/A N/A N/A
Decision Rule

PMID:21372037

Additional Study-Specific Protocols
Study-Specific Publications

No study-specific publications defined.

Study-Specific Resources

No study-specific resources defined.

SPORE/EDRN/PRE-PLCO Ovarian Phase II Validation Study

Create a new set of phase II specimens (160 cases with pre-operative bloods representing major histologic types and including 80 early-staged and 80 late-staged cases, 160 controls with benign disease, 480 general population controls, and a small set of serial Samples collected either at least 3 months apart, but not more than 6 months apart OR between 10 months apart and no more than 14 months apart in 40 healthy controls) will be used to evaluate markers identified in preliminary work. The top 5-10 markers, plus an expanded panel of Luminex markers, will comprise a “working consensus panel” for subsequent analysis in PLCO specimens.

View more about this study
Biomarker Characteristics Summary
Notes Sensitivity Specificity Prevalence NPV PPV Specific Assay Type
For all cases, using all controls. Results from preliminary analysis, 50% of 114 sample set. Daniel Cramer laboratory. 38.0 95.0 N/A N/A N/A
For early stage (more than 12 months prior to diagnosis), using all controls. Results from preliminary analysis, 50% of 114 sample set. Daniel Cramer laboratory. 51.0 95.0 N/A N/A N/A
For late stage (within 12 months of diagnosis), using all controls. Results from preliminary analysis, 50% of 114 sample set. Daniel Cramer laboratory. 17.0 95.0 N/A N/A N/A
Cases chosen with diagnosis of ovarian cancer (on average) 9 months prior. Controls were matched to cases by age and timing of specimen collection including general population controls (50%), false positive CA125 (25%), and family history of breast cancer (25%). All cases (n=60). 42.0 95.0 N/A N/A N/A
Cases diagnosed <= 6 months after draw (n=25). 68.0 95.0 N/A N/A N/A
Cases diagnosed > 6 months after draw (n=35). 23.0 95.0 N/A N/A N/A
Decision Rule

PMID:21372037

Additional Study-Specific Protocols
Study-Specific Publications

No study-specific publications defined.

Study-Specific Resources

No study-specific resources defined.

Validation of Early Detection Ovarian Cancer Biomarkers (Team Project)

Early detection of Ovarian Cancer (OC) is one of the key clinical problems in this disease. We propose a team EDRN project to address the issue of early detection of OC by performing a validation study on candidate protein markers already identified in previous EDRN research or in the literature (e.g. protein products of TCGA identified mutations specific to ovarian cancer). (See appendix for full listing) Biospecimen sources have been identified which include samples obtained at diagnosis and matched controls (Urban, Godwin, Marks, Skates), and longitudinal samples obtained prior to diagnosis (Urban, Skates, Godwin). Bioinformatic filters will be applied to rank the candidates (Diamandis). In order of ranking, candidate proteins for which high quality antibodies are available will be measured by development of ELISAs at JHU (Chan/Zhang) or through NAPPA at DFCI (Anderson/LaBaer), while for other candidates mass spectrometry based selective reaction monitoring (SRM) assays will be developed at PNNL (Rodland). Three milestones are defined. The first two milestones are to assemble the necessary specimens and to develop the qualifying assay(s). The final milestone is to estimate the markers’ sensitivity one year prior to diagnosis at a given high specificity.

View more about this study
Biomarker Characteristics Summary

No statistics found.

Decision Rule

No extra decision rule information available

Additional Study-Specific Protocols
Study-Specific Publications

No study-specific publications defined.

Study-Specific Resources

No study-specific resources defined.

Organ-Specific Protocols

No organ-specific protocols defined.

Organ-Specific Publications

Organ-Specific Resources

No organ-specific resources defined.

Resources

External Resources for HE4

This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in sperm maturation.

Gene

Protein

Other

Biomuta

Mutation Statistics

Gene Name: WFDC2
UniProt Accession #: Q14508
Mutated Sites Count: 17
Associated Pubmed ID Count 1
CancerDO Count 9
Affected Protein Function Sites Count: 4

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