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This biomarker is also known as:
  • Hyperplastic polyposis protein 1,
  • TENB2,
  • Tomoregulin-2,
  • TR-2,
  • CT120.2,
  • cancer/testis antigen family 120, member 2,
  • TR,
  • TPEF,
  • HPP1,
  • transmembrane protein TENB2,
  • transmembrane protein with EGF-like and two follistatin-like domains 2,
  • tomoregulin,


HPP1 (also called TMEFF2) may be a survival factor for hippocampal and mesencephalic neurons. The shedded form (generated by proteolytic shedding) up-regulates cancer cell proliferation, probably by promoting ERK1/2 phosphorylation. HPP1 is down-regulated in tumor cell lines in response to a high level of methylation in the 5' region. The CpG island methylation correlates with HPP1 silencing in tumor cell lines.


QA State: Accepted
Type: Genomic
Short Name:


The following organs have data associated with this biomarker…



Phase: Two
QA State: Accepted


Esophageal adenocarcinoma risk in Barrett's esophagus is increased 30- to 125- fold versus the general population. Among all Barrett's esophagus patients neoplastic progression occurs only once per 200 patient-years. Molecular markers (individual or in panel) would be useful to risk-stratify patients for more efficient surveillance endoscopy and to improve the early detection of progression.

Performance Comment

p16, RUNX3, and TMEFF2 (HPP1) display increasing methylation frequencies in Barrett's esophagus versus esophageal adenocarcinoma. These markers are being further investigated for potential utility in screening Barrett's patients likely to develop esophageal adenocarcinoma.

Supporting Study Data

The following studies/protocols provide evidence supporting TMEFF2 indications for the Esophagus…

Barrett's Esophagus Methylation Profiles

We propose a nested case-control study of biomarkers in the setting of BE. By bringing together research institutions with large populations of patients with BE, we will perform a multi-center study of FISH and hypermethylation markers as possible prognostic factors in BE. The centers will select from their cohorts who have progressed to HGD or to adenocarcinoma of the esophagus ("progressors"), and who also donated samples prior to the development of cancer, when their histology was felt to be benign. These subjects will be compared to individuals who have been under endoscopic surveillance, but who have not progressed to HGD or EAC ("non-progressors"). Using this approach, we hope to identify promising markers for risk stratification in BE. We expect to be able to make successful application for a prospective study of markers identified in this case-control study.

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Biomarker Characteristics Summary
Notes Sensitivity Specificity Prevalence NPV PPV Specific Assay Type
Assessment of the classification accuracy of a single marker using ROC curve analyses show AUC for HPP1, p16, and RUNX3 are all significantly greater than 0.50. For HPP1, AUC (95% confidence interval) was 0.647 (0.556, 0.739). N/A N/A N/A N/A N/A
Decision Rule


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

No organ-specific publications defined.

Organ-Specific Resources

No organ-specific resources defined.


Mutation Statistics

Gene Name: TMEFF2
UniProt Accession #: Q9UIK5
Mutated Sites Count: 69
Associated Pubmed ID Count 12
CancerDO Count 22
Affected Protein Function Sites Count: 1

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