Aliases:This biomarker is also known as:
- Hyperplastic polyposis protein 1,
- transmembrane protein with EGF-like and two follistatin-like domains 2,
- transmembrane protein TENB2,
- cancer/testis antigen family 120, member 2,
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.
The following organs have data associated with this biomarker…
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.
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.View more about this study
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|
Additional Study-Specific Protocols
No study-specific publications defined.
No study-specific resources defined.
No organ-specific protocols defined.
No organ-specific publications defined.
No organ-specific resources defined.
- Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors.
- HPP1: a transmembrane protein-encoding gene commonly methylated in colorectal polyps and cancers.
- Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features.
- Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma.
- Distinct TPEF/HPP1 gene methylation patterns in gastric cancer indicate a field effect in gastric carcinogenesis.
External Resources for TMEFF2
|UniProt Accession #:||Q9UIK5|
|Mutated Sites Count:||82|
|Associated Pubmed ID Count||14|
|Affected Protein Function Sites Count:||5|