Biomarker: HIF-1alpha

Histology type: endometrioid endometrial carcinoma

Country: Japan

Region: Gifu City

Followed up time :

Subgroup 1 name : type1

Subgroup 1 number: 108

Subgroup 2 name: type2

Subgroup 2 number: 41

Conclusion: HIF-1alpha may play an important role in endometrial adenocarcinoma progression, particularly in type I endometrial adenocarcinoma. Additional investigations of HIF-1alpha as a biomarker of aggressive potential and as a novel target for therapeutics in endometrial adenocarcinoma are warranted.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : Increased expression

Expression elevation: Expression of HIF-1a was assessed by analyzing at least 1000 tumor cells from tumor fields, and the labeling index was calculated as the percentage of labeled nuclei of the total number of tumor cells that were counted. HIF-1a expression was considered low if 410% but o45% (median value) of cells showed positive nuclear or cytoplasmic staining, those with 445% (median value) were considered to have high expression

Statictics: Mean ;Range

Subgroup 1 age: 61;38–79

Subgroup 2 age: 67;56–83

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).

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). (Microbial infection) In monocytes, human coronavirus SARS-CoV-2 increases HIF1A levels and activity which promotes a pro-inflammatory state.

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: HIF1A protein expression summary - The Human Protein Atlas

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

Expression figure legend: High expression of HIF-1α in type I endometrial adenocarcinoma (a; × 400) and type II endometrial adenocarcinoma

Expression figure link: https://www.nature.com/articles/3800718/figures/1

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