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CA125

Basics

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

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:
HGNC Name: MUC16

Organs

The following organs have data associated with this biomarker…

Breast

Attributes

Phase: One
QA State: Curated

Overview

Performance Comment

Ninety biomarkers were measured using a series of multiplexed immunoassays and results analyzed by the EDRN data management center splitting the cases and controls into training and validation sets, excluding subjects with DCIS or atypical hyperplasia from the training phase. We found little evidence that any of these markers can discriminate women with invasive cancer from those with benign breast conditions.

Supporting Study Data

The following studies/protocols provide evidence supporting CA125 indications for the Breast…

Breast Reference Set Application: Anu Mathew-Meso Scale (2012)

Using a subset of plasma samples (n=505) from the reference set, we analyzed 90 proteins by multiplexed immunoassays for their potential utility as diagnostic markers.

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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

No organ-specific publications defined.

Organ-Specific Resources

No organ-specific resources defined.

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…

Phase II Validation of a New Panel of Biomarkers for Early Detection of Ovarian Cancer

While all cancer patients could potentially benefit from earlier detection and prevention, the development of new screening technologies and chemoprevention for epithelial ovarian cancer (EOC) is unique in this regard. EOC is characterized by few early symptoms, presentation at an advanced stage, and poor survival. Presently there is no commercially available test that is diagnostic for either early or advanced stage epithelial ovarian cancer. The most commonly used marker, CA125, identifies a group of cell surface glycoproteins, which have uncertain biological behavior and very limited clinical utility for the detection of early stage disease. In recent years, several approaches have been used in order to develop a test for early detection, including the analysis of serum samples by SELDI-TOF and MALDI-TOF to find proteins or protein fragments of unknown identity that detect the presence/absence of cancer. Unfortunately, at the present time, none of these techniques have been shown to be adequate. Therefore, the development of a test that can detect early stages of the disease could dramatically improve treatment success and long-term survival. We have developed a new blood test based on a different approach: 1) we used known proteins related to cancer biology, 2) we characterized these proteins with several different screening steps using samples obtained from both healthy and cancer patient populations, and 3) validated the results with different techniques. Using split point analysis with four markers, 96 out of 100 EOC patients (96%) were correctly diagnosed with ovarian cancer (including 23 of 24 patients with Stage I/II EOC). In the healthy group, 6 out of 106 individuals were diagnosed incorrectly (5.6%). Working in collaboration with the Early Detection Network (EDRN/NCI/NIH), we performed Phase I discovery study confirming the potential application of this test for early detection of ovarian cancer (Preliminary results). The main objective of this pr

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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.

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.

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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

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.

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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

No study-specific publications defined.

Study-Specific Resources

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 CA125

This gene encodes a protein that is a member of the mucin family. Mucins are high molecular weight, O-glycosylated proteins that play an important role in forming a protective mucous barrier, and are found on the apical surfaces of the epithelia. The encoded protein is a membrane-tethered mucin that contains an extracellular domain at its amino terminus, a large tandem repeat domain, and a transmembrane domain with a short cytoplasmic domain. The amino terminus is highly glycosylated, while the repeat region contains 156 amino acid repeats unit that are rich in serines, threonines, and prolines. Interspersed within the repeats are Sea urchin sperm protein Enterokinase and Agrin (SEA) modules, leucine-rich repeats and ankyrin (ANK) repeats. These regions together form the ectodomain, and there is a potential cleavage site found near an SEA module close to the transmembrane domain. This protein is thought to play a role in forming a barrier, protecting epithelial cells from pathogens. Products of this gene have been used as a marker for different cancers, with higher expression levels associated with poorer outcomes.

Gene

Protein

Other

Biomuta

Mutation Statistics

Gene Name: MUC16
UniProt Accession #: Q8WXI7
Mutated Sites Count: 2
Associated Pubmed ID Count 1
CancerDO Count 1
Affected Protein Function Sites Count: 1

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