Biomarker: FOXA1

Histology type: endometrial carcinoma

Country: Norway

Region: Bergen

Study type: prospective study

Followed up time :

Subgroup 1 name : High

Subgroup 1 number: 203

Subgroup 2 name: Low

Subgroup 2 number: 326

Conclusion: Low FOXA1 is associated with poor survival and suggests a potential for HDAC inhibitors in endometrial carcinoma. A switch in FOXA1 expression from primary to metastatic lesions is observed and gene expression indicates a link between FOXA1 and CDKN2A in metastatic lesions.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : low expression( staining index was calculated as the product of intensity and staining area.)

Expression elevation: HC staining was evaluated using a semiquantitative system where both intensity of the staining, and area of tumor cells with positive staining were considered. Staining intensity was graded from 0 (no staining) to 3 (strong staining). Proportion of stained tumor cells was graded as 0, 1 (<10%), 2 (10% to 50%) and 3 (>50%). A staining index was calculated as the product of intensity and staining area. In the statistical analysis, staining indexes for FOXA1 were categorized in tertiles considering the frequency distribution for the marker, size of subgroups and the number of events in each category. When evaluating heterogenic multiple metastatic lesions form the same patient, FOXA1 was defined as low if any of the metastatic lesions demonstrated low expression.

Statictics: cutoff<66;cutoff>66

Cohort age: 278;251

Subgroup 1 age: 118;85

Subgroup 2 age: 160;166

Funtion Uniprot: Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Its differential recruitment to chromatin is dependent on distribution of histone H3 methylated at 'Lys-5' (H3K4me2) in estrogen-regulated genes. Involved in the development of multiple endoderm-derived organ systems such as liver, pancreas, lung and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles (By similarity). Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription; required for ESR1 binding to the NKX2-1 promoter in breast cancer cells; binds to the RPRM promoter and is required for the estrogen-induced repression of RPRM. Involved in regulation of apoptosis by inhibiting the expression of BCL2. Involved in cell cycle regulation by activating expression of CDKN1B, alone or in conjunction with BRCA1. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis

UniProt ID: P55317

UniProt Link: https://www.uniprot.org/uniprotkb/P55317/entry

Biological function from UniProt: #Transcription #Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Highly expressed in prostate and ESR1-positive breast tumors. Overexpressed in esophageal and lung adenocarcinomas.

Subcellular UniProt: #Nucleus

Alternative name from UniProt:

Recommended name: Hepatocyte nuclear factor 3-alpha

Gene name from HGNC: HSF1 (HSTF1)

HPA class: Cancer-related genes Plasma proteins Transcription factors

AlphaFold DB: P55317

AlphaFold Link: https://www.uniprot.org/uniprotkb/P55317/entry#structure

HPA link: https://www.proteinatlas.org/ENSG00000129514-FOXA1

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 human brain regional 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

Pathology endo: https://www.proteinatlas.org/ENSG00000185122-HSF1/pathology/endometrial+cancer

Survival figure legend: FOXA1 and survival.$ FOXA1 survival analyses stratified for ERα status in the tumors.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029819/figure/pone-0098069-g001/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029819/figure/pone-0098069-g002/

OMIM: 602294

OMIM link2: https://www.omim.org/entry/602294

HGNC ID: HGNC:5021

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:5021