Skip to content. | Skip to navigation

National Cancer Institute U.S. National Institutes of Health www.cancer.gov

Navigation

Personal tools

You are here: Home / Biomarkers / HE4

HE4

Basics

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

View in BioMuta

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:

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

The obvious appeal of a strategy for the early detection of ovarian cancer is based upon the tendency for the disease to present at advanced stages associated with poor survival. If the diagnosis could be largely shifted to stages I or II associated with survival close to 90%, then the overall mortality for this disease could be dramatically altered without any advances in therapy. While approaches to ovarian cancer screening might include pelvic examination or sonography, a vast amount of information exists on potential blood markers for the disease. The precision of sensitivity and specificity estimates will be greater for larger versus smaller study populations; but the effect produced by differences in the populations studied cannot as easily be predicted. Most of the studies relied on phase II validation (i.e. case vs. control differences); but case groups may differ by disease stage and histology that may affect overall estimates of sensitivity. Many studies have limited case specimens to those collected pre-operatively, but not all were explicit in this regard. Few studies have used pre-diagnostic sera months or years before diagnosis, so-called Phase III studies. Similarly, the nature of the control group will also affect specificity estimates. Inclusion of surgical controls that have benign gynecological conditions such as fibroids, endometriosis, or benign ovarian tumors may elevate marker levels and lower specificity. One strategy, besides combining markers, to improve the sensitivity and/or specificity would be to use marker history in the context of serial testing. Elevated but declining marker levels would indicate a transient condition associated with marker production. Elevated but stable levels might indicate chronic but benign conditions associated with marker production, while elevated and increasing levels are more likely indicative of cancer. Our hypothesis is that a panel of biomarkers will have better performance characteristics as a screening test for pre-clinical ovarian cancer than any single marker, and yield a longer lead time than CA125 alone.

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
Study-Specific Resources

No study-specific resources defined.

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

Phase II specimens from 160 ovarian cancer cases and 640 benign disease or general population controls were assembled from four Early Detection Research Network (EDRN) or Ovarian Cancer Specialized Program of Research Excellence (SPORE) sites and used to rank 51 biomarkers. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40.

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
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.

News

The final report of the 2013 Cancer Biomarkers Bioinformatics Workshop is now available.

Announcement 03/06/2014

Thank you to everyone who helped make the 27th EDRN Steering Committee Meeting a success. We look forward to seeing everyone at the 9th EDRN Scientific Workshop from September 8-11, 2014 in Washington D.C.

Announcement