Biomarker: HSF1

Histology type: endometrial carcinoma

Country: Norway

Region: Bergen

Study type: prospective study

Followed up time :

Subgroup 1 name : 0–4

Subgroup 1 number: 166

Subgroup 2 name: 6;9

Subgroup 2 number: 307;163

Conclusion: We demonstrate for the first time in endometrial cancer that high expression of HSF1 and measures for transcriptional activation of HSF1 associate with poor outcome and disease progression.

Sample type : tissue

Sample method: immunohistochemistry ,Gene expression analyses,

Expression pattern : high expression ( index 9,a staining index was calculated as a product of staining intensity (0–3) and area of positive tumour cells (1⩽10%, 2=10%–50% and 3⩾50%). )

Expression elevation: A staining index was calculated as a product of staining intensity (0–3) and area of positive tumour cells (1⩽10%, 2=10%–50% and 3⩾50%). In subsequent statistical analyses, indexes were grouped in tertiles, considering the size of the subgroups and the number of events in each category. Tertile division was selected according to similarity in survival inside each tertile. Index 0–4 was considered low, index 6 intermediate and index 9 was considered high.

Statictics: cutoff<66;cutoff>66

Subgroup 1 age: 93;75

Subgroup 2 age: 176;33;71;92

Funtion Uniprot: Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones heat shock proteins (HSPs) that protect cells from cellular insults' damage (PubMed:1871105, PubMed:11447121, PubMed:1986252, PubMed:7760831, PubMed:7623826, PubMed:8946918, PubMed:8940068, PubMed:9341107, PubMed:9121459, PubMed:9727490, PubMed:9499401, PubMed:9535852, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:25963659, PubMed:26754925, PubMed:18451878). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:9727490, PubMed:11583998, PubMed:16278218). Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes (PubMed:1871105, PubMed:1986252, PubMed:8455624, PubMed:7935471, PubMed:7623826, PubMed:8940068, PubMed:9727490, PubMed:9499401, PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:25963659, PubMed:26754925). Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival (PubMed:18451878). Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form (PubMed:11583998, PubMed:16278218). Binds to inverted 5'-NGAAN-3' pentamer DNA sequences (PubMed:1986252, PubMed:26727489). Binds to chromatin at heat shock gene promoters (PubMed:25963659). Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells (PubMed:9341107). Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner (PubMed:14707147). Plays a role in nuclear export of stress-induced HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of mitotic progression (PubMed:18794143). Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner (PubMed:26359349). Involved in stress-induced cancer cell proliferation in a IER5-dependent manner (PubMed:26754925).28 Publications (Microbial infection) Plays a role in latent human immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to the HIV-1 long terminal repeat promoter (LTR) to reactivate viral transcription by recruiting cellular transcriptional elongation factors, such as CDK9, CCNT1 and EP300.

UniProt ID: Q00613

UniProt Link: https://www.uniprot.org/uniprotkb/Q00613/entry

Biological function from UniProt: #DNA damage #DNA repair #Host-virus interaction #mRNA processing #mRNA transport

Molecular function from UniProt:

Subcellular UniProt: #Centromere #Chromosome #Cytoplasm #Cytoskeleton #Kinetochore #Nucleus

Alternative name from UniProt:

Recommended name: Heat shock factor protein 1

Gene name from HGNC: HSF1 (HSTF1)

HPA class: Cancer-related genes Plasma proteins Transcription factors

AlphaFold DB: Q00613

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q00613

HPA link: https://www.proteinatlas.org/ENSG00000185122-HSF1

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: General nuclear expression.

Single cell type specificity Cell type enhanced (Early spermatids)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm, Cytosol

Cancer prognostic summary HPA Prognostic marker in liver cancer (unfavorable) and endometrial cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000185122-HSF1/pathology

Expression figure legend: Heat shock factor 1 (HSF1) is associated with aggressive disease in endometrial cancer.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090731/figure/fig1/

Survival figure legend: Heat shock factor 1 (HSF1) level predicts outcome in ERα-positive and -negative subgroups. $ Heat shock factor 1 (HSF1)-related cancer programme is linked to poor prognosis in endometrial cancer.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090731/figure/fig2/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090731/figure/fig3/

OMIM: 140580

OMIM link2: https://www.omim.org/entry/140580

HGNC ID: HGNC:5224

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5224