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B7-H4

Basics

Aliases:
This biomarker is also known as:
  • Immune costimulatory protein B7-H4,
  • B7 family member, H4,
  • VCTN1,
  • B7X,
  • B7h.5,
  • DD-0110,
  • PRO1291,
  • V-set domain containing T cell activation inhibitor 1,
  • B7 superfamily member 1,
  • T-cell costimulatory molecule B7x,
  • FLJ22418,
  • OV110,
  • B7S1,
  • Protein B7S1,
  • B7H4,
  • VTCN1,

View in BioMuta

Description…

Highly glycosylated sialomucin; expressed on immune cells. Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. Involved in promoting epithelial cell transformation. Overexpressed in breast, ovarian, endometrial, renal cell (RCC) and non-small-cell lung cancers (NSCLC). Belongs to the B7 family of costimulatory proteins.

Attributes

QA State: Accepted
Type: Protein
Short Name:
HGNC Name: VTCN1

Organs

The following organs have data associated with this biomarker…

Ovary

Attributes

Phase: Three
QA State: Accepted

Overview

Genomic analysis revealed upregulation in breast and ovarian epithelial tumors; protein overexpression studies confirmed finding.

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. B7-H4 alone was not a strong predictor.

Supporting Study Data

The following studies/protocols provide evidence supporting B7-H4 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). 25.0 95.0 N/A N/A N/A
Cases diagnosed <= 6 months after draw (n=25). 48.0 95.0 N/A N/A N/A
Cases diagnosed > 6 months after draw (n=35). 6.0 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
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). 25.0 95.0 N/A N/A N/A
Cases diagnosed <= 6 months after draw (n=25). 48.0 95.0 N/A N/A N/A
Cases diagnosed > 6 months after draw (n=35). 6.0 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.

Announcement 10/07/2014

EDRN Patient Advocates will host an EDRN Advocacy Educational Webinar, Biomarkers for Prostate Cancer Detection and Monitoring, on Monday, January 12th, 2015, at 1 p.m. EDT / 10 a.m. PDT. Registration is not required for this. Please click for more information.
Announcement 09/14/2014

Thank you to everyone who helped make the 9th EDRN Scientific Workshop a success. We look forward to seeing everyone at the 28th EDRN Steering Committee Meeting from March 31-April 2, 2015, in Atlanta, GA.