Biomarker: HIF-1α

Histology type: endometrial carcinoma

Stage: advanced stage

Region: Minia

Followed up time :

Subgroup 1 name : negative

Subgroup 1 number: 30

Subgroup 2 name: positive

Subgroup 2 number: 65

Conclusion: HIF-1α proteins are promising potential prognostic biomarkers in endometrial carcinomas since their overexpression is associated with clinicopathologic variables of advanced disease

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : overexpression ( total score was ≥3)

Expression elevation: Positive immunostaining of PD-L1 was membranous, and HIF-1α was nuclear. Positive cases were classified according to the rate (percentage) of positive cell staining (R) on the one hand and their staining intensity (I) on the other hand. Immunostaining of <10% of tumor cells is categorized as 0, immunostaining of 10%–25% of tumor cells as 1, staining of 26%–50% of tumor cells as 2, staining of 51%–75% as 3, and staining of >75% as 4. The staining intensity in each specimen was categorized as 1, 2, and 3 (weak, moderate, or strong, respectively). The total immunostaining score (I × R) was assigned to each case by multiplying the score for the percentage of positive tumor cells (1–4) by staining intensity score (1–3) resulting in a total score of 1–12. For statistical purposes, the investigated cases were categorized as negative if the total score was <3 and positive if the total score was ≥3.

Statictics: cutoff<50;cutoff>50

Cohort age: 41;54

Subgroup 1 age: 16;14

Subgroup 2 age: 25;40

Funtion Uniprot: Hydroxylates HIF-1 alpha at 'Asn-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation

UniProt ID: Q9NWT6

UniProt Link: https://www.uniprot.org/uniprotkb/Q9NWT6/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Subcellular UniProt: #Cytoplasm #Nucleus

Alternative name from UniProt:

Recommended name: Hypoxia-inducible factor 1-alpha inhibitor

Gene name from HGNC: HIF1A (bHLHe78, HIF-1alpha, HIF1, MOP1, PASD8)

HPA class: Cancer-related genes Human disease related genes Metabolic proteins Plasma proteins Transcription factors

AlphaFold DB: Q9NWT6

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q9NWT6

HPA link: https://www.proteinatlas.org/ENSG00000100644-HIF1A

Tissue specificity RNA from HPA: Tissue enhanced (bone marrow)

Tissue expression from HPA: Mainly nuclear expression with cases of cytoplasmic expression. Including chromosome alignment expression in a subset of cells in gallbladder.

Single cell type specificity Granulosa cells - Unknown function (mainly)

Immune cell specificity: Immune cell enhanced (eosinophil)

Subcellular summary HPA Located in Nucleoplasm, Nuclear bodies

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000100644-HIF1A/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000100644-HIF1A/pathology/endometrial+cancer

OMIM: 606615

OMIM link2: https://www.omim.org/entry/606615

HGNC ID: HGNC:4910

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4910