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CA125

Basics

Aliases:
This biomarker is also known as:
  • CA125 ovarian cancer antigen,
  • CA-125,
  • Ovarian cancer-related tumor marker CA125,
  • MUC16,
  • FLJ14303,
  • mucin 16, cell surface associated,
  • Ovarian carcinoma antigen CA125,
  • Mucin-16,
  • Mucin 16,
  • MUC-16,

View in BioMuta

Description…

MUC16 (CA125) is a highly glycosylated sialomucin that is expressed on epithelial cell surface, especially on ovarian cancer cells. MUC16 is anchored to the epithelium by a transmembrane domain and is released into the extracellular space by enzymatic cleavage. It is thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces.

Attributes

QA State: Accepted
Type: Protein
Short Name:

Organs

The following organs have data associated with this biomarker…

Ovary

Attributes

Phase: Three
QA State: Accepted

Overview

The best known marker for late stage and to a lesser degree early stage ovarian carcinomas - especially of serous and endometrioid histology. Overexpressed in ovarian carcinomas and ovarian low malignant potential (LMP) tumors as compared to the expression in normal ovarian tissue and ovarian adenomas. CA125, an epithelial sialomucin also called MUC16, is a heavily glycosylated protein with relatively high molecular weight and is the only approved marker for monitoring ovarian cancer. Although sialomucins are transmembrane in location, they can be found in serum. Most of the markers in this category have been identified through approaches in which human cancer cells are used as an antigenic stimulus in animals to raise antibodies, which can then efficiently detect the antigen in human serum. CA125 is the best documented and best performing single marker among the epithelial sialomucins. CA125 can be elevated in early pregnancy and with endometriosis, fibroids or infections of the genital tract. These conditions would affect specificity of the test and the possibility of false positive results.

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.

Supporting Study Data

The following studies/protocols provide evidence supporting CA125 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
The dataset contains the original values and the log transformed values for CA125, CA15.3, CA19.9, CA72.4, KLK6 (aka HK6), HE4, and OV110 (aka B7-H4). Created by Allison Vitonis. Partners used plate-based assay for B7-H4(Diadexus), HE4, and Kallikrein 6 (as described in (Diamandis EP, Scorilas A, Fracchioli S, Van Gramberen M, De Bruijn H, Henrik A, Soosaipillai A, Grass L, Yousef GM, Stenman UH, Massobrio M, Van Der Zee AG, Vergote I, and Katsaros D, Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J Clin Oncol, 2003. 21(6): p. 1035-43)). Platform-based assays (Roche) were used for CA125, CA15.3, CA72.4 and CA19.9. Unless the volume was insufficient assays were run in duplicate and averaged. These seven markers were chosen based on their performance in the phase II (pre-PLCO) data. This data us available in the file entitle "Harvard_markers_11132008.xls" which is linked to this record on the MUC16 Basics Tab. N/A N/A 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). 41.0 95.0 N/A N/A N/A
Cases diagnosed <= 6 months after draw (n=25) 79.0 95.0 N/A N/A N/A
Cases diagnosed > 6 months after draw (n=35) 15.0 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
The dataset contains the original values and the log transformed values for CA125, CA15.3, CA19.9, CA72.4, KLK6 (aka HK6), HE4, and OV110 (aka B7-H4). Created by Allison Vitonis. Partners used plate-based assay for B7-H4(Diadexus), HE4, and Kallikrein 6 (as described in (Diamandis EP, Scorilas A, Fracchioli S, Van Gramberen M, De Bruijn H, Henrik A, Soosaipillai A, Grass L, Yousef GM, Stenman UH, Massobrio M, Van Der Zee AG, Vergote I, and Katsaros D, Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J Clin Oncol, 2003. 21(6): p. 1035-43)). Platform-based assays (Roche) were used for CA125, CA15.3, CA72.4 and CA19.9. Unless the volume was insufficient assays were run in duplicate and averaged. These seven markers were chosen based on their performance in the phase II (pre-PLCO) data. This data us available in the file entitle "Harvard_markers_11132008.xls" which is linked to this record on the MUC16 Basics Tab. N/A N/A 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. 50.0 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. N/A 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). 41.0 95.0 N/A N/A N/A
Cases diagnosed <= 6 months after draw (n=25) 79.0 95.0 N/A N/A N/A
Cases diagnosed > 6 months after draw (n=35) 15.0 95.0 N/A N/A N/A
Decision Rule

PMID:21372037

Additional Study-Specific Protocols
Study-Specific Publications
Study-Specific Resources

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 06/26/2014


Please click here to register for the 9th EDRN Scientific Workshop from September 8-10, 2014, in Bethesda, Maryland. The meeting registration page also has agendas and hotel reservation information.
Announcement 06/05/2014


Funding Opportunity Available

Both RFAs for Molecular and Cellular Characterization of Screen-Detected Lesions have been published.

RFA-CA-14-010.html

and

RFA-CA-14-011.html