Biomarker: EphA2

Histology type: endometrioid endometrial carcinoma

Country: USA

Region: Texas

Followed up time :

Subgroup 1 name : Low EphA2 in benign

Subgroup 1 number: 9

Subgroup 2 name: High EphA2 in benign

Subgroup 2 number: 1

Conclusion: EphA2 overexpression was associated with aggressive phenotypic features in EEC and was associated inversely with ER and PR expression. Thus, EphA2 may be an important therapeutic target, especially in patients with hormone receptor-negative endometrial carcinoma.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : overexpression(SI = 9-12)

Expression elevation: Semi-quantitative assessment of immunohistochemical expression was performed as previously described (11) by assessing the percentage of stained tumor cells and staining intensity. Briefly, the percentage of positively stained cells was rated as follows: 0 points, 0-5%; 1 point, 6-50%; 2 points, 51-75%; 3 points, >75%. The staining intensity was rated in the following manner: 2 points, weak intensity; 3 points, moderate intensity; 4 points, strong intensity. The product of the scores for intensity and percentage of positive cells were used to get an overall score index (SI) ranging from 0-3. Tumors were categorized into 3 groups based on the SI: negative or weak expression (SI of 0-4), moderate expression (SI of 5-8) and strong expression (SI of 9-12). low expression (negative, weak or moderate staining; SI= 0-8) and high expression (strong staining; SI = 9-12).

Statictics: Mean ;Range

Cohort age: 63;27 - 91

Funtion Uniprot: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.9 Publications (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins.1 Publication

UniProt ID: P29317

UniProt Link: https://www.uniprot.org/uniprotkb/P29317/entry

Biological function from UniProt: #Angiogenesis #Apoptosis #Cell adhesion #Differentiation #Host-virus interaction

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g. skin, intestine, lung, and ovary.

Subcellular UniProt: #Cell junction #Cell membrane #Cell projection #Membrane

Alternative name from UniProt:

Catalytic activity: ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]

Recommended name: Ephrin type-A receptor 2

Gene name from HGNC: EPHA2 (ECK)

HPA class: Cancer-related genes Disease related genes Enzymes FDA approved drug targets Human disease related genes Metabolic proteins RAS pathway related proteins

AlphaFold DB: P29317

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P29317

Induction: Up-regulated by UV irradiation via a TP53-independent, MAPK-dependent mechanism.

HPA link: https://www.proteinatlas.org/ENSG00000142627-EPHA2

Tissue specificity RNA from HPA: Tissue enhanced (esophagus)

Single cell type specificity Cell type enhanced (Suprabasal keratinocytes, Basal keratinocytes, Urothelial cells, Glandular and luminal cells, Squamous epithelial cells)

Immune cell specificity: Immune cell enriched (plasmacytoid DC)

Subcellular summary HPA Located in Nuclear speckles, Golgi apparatus, Plasma membrane, Cell Junctions (CCD Transcript)

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000142627-EPHA2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000142627-EPHA2/pathology/endometrial+cancer

Phenotype ID: 116600

Disease: Cataract 6, multiple types (CTRCT6);o disease ID;

Note1: The disease is caused by variants affecting the gene represented in this entry;Overexpressed in several cancer types and promotes malignancy;

Note2: A number sign (#) is used with this entry because multiple types of cataract are caused by heterozygous mutation in the EPHA2 gene (176946) on chromosome 1p36.

OMIM: 176946; 116600;

OMIM link1: https://www.omim.org/entry/116600

OMIM link2: https://www.omim.org/entry/176946;https://www.omim.org/entry/116600

Phenotype: CATARACT 6, MULTIPLE TYPES

HGNC ID: HGNC:3386

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3386