Biomarker: hypoxia-inducible factor 1α

Histology type: endometrioid endometrial carcinoma

Stage: aggressive phenotype

Country: China

Region: Shanghai

Study type: retrospective study

Followed up time :

Subgroup 1 name : negative

Subgroup 1 number: 43

Subgroup 2 name: positive

Subgroup 2 number: 81

Conclusion: These results demonstrated for the first time that the hypoxia-inducible factor 1α/TWIST/E-cadherin pathway may play a critical role in invasion and metastasis of endometrioid endometrial carcinoma. The combined evaluation of these markers may be useful in predicting aggressive phenotypes and thus prognosis in patients with endometrioid endometrial carcinoma.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : expression (hypoxia-inducible factor 1α+TWIST+E-cadherin )

Expression elevation: The sum of the intensity and extent points was used as the final staining scores (0 – 7),preserved E-cadherin expression (score 3) or reduced E-cadherin expression (scores 0, 1 and 2).

Statictics: cutoff<50;cutoff>50

Cohort age: 29;95

Funtion Uniprot: Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:9887100, PubMed:16543236). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298).By Similarity14 Publications (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943).1 Publication

UniProt ID: Q16665

UniProt Link: https://www.uniprot.org/uniprotkb/Q16665/entry

Biological function from UniProt: #Host-virus interaction #Transcription #Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. A higher level expression seen in pituitary tumors as compared to the pituitary gland.

Subcellular UniProt: #Cytoplasm #Nucleus

Alternative name from UniProt:

Activity regulation: Induced by reactive oxygen species (ROS).1 Publication (Microbial infection) In monocytes, human coronavirus SARS-CoV-2 increases HIF1A levels and activity which promotes a pro-inflammatory state.1 Publication

Recommended name: Hypoxia-inducible factor 1-alpha

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: Q16665

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q16665

Induction: Under reduced oxygen tension. Induced also by various receptor-mediated factors such as growth factors, cytokines, and circulatory factors such as PDGF, EGF, FGF2, IGF2, TGFB1, HGF, TNF, IL1B/interleukin-1 beta, angiotensin-2 and thrombin. However, this induction is less intense than that stimulated by hypoxia. Repressed by HIPK2 and LIMD1.

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 Low cell type specificity

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: 603348

OMIM link2: https://www.omim.org/entry/603348

HGNC ID: HGNC:4910

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