Biomarker: ALDH1

Histology type: endometrioid endometrial carcinoma

Country: USA

Region: UCLA

Study type: retrospective

Followed up time :

Subgroup 1 name : negative

Subgroup 1 number: 105

Subgroup 2 name: positive

Subgroup 2 number: 53

Conclusion: ALDH1 expression predicts progression of premalignant lesions to cancer in Type I endometrial carcinomas

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : expression

Expression elevation: Rating the intensity from 0 to 3 (0 = below the level of detection, 1 = weak, 2 = moderate, 3 = strong) and percentage of cells staining at each intensity. A histologic score (H-score) was calculated for each sample by multiplying the percentage of positive cells by the intensity score. For cytoplasmic and nuclear expression, positive ALDH1 expression was defined as an H-score being larger than 0.

Statictics: Mean (SD);Range

Cohort age: 56;30–86

Subgroup 1 age: 60;30–79

Subgroup 2 age: 55 ;35–86

Funtion Uniprot: Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:19296407, PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:26373694, PubMed:25450233). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (By similarity). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:19296407, PubMed:12941160, PubMed:15623782). Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (PubMed:17175089). Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity).

UniProt ID: P00352

UniProt Link: https://www.uniprot.org/uniprotkb/P00352/entry

Biological function from UniProt: #Lipid metabolism

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed by erythrocytes (at protein level).

Subcellular UniProt: #Cell projection #Cytoplasm

Alternative name from UniProt:

Catalytic activity: an aldehyde + H2O + NAD+ = a carboxylate + 2 H+ + NADH,all-trans-retinal + H2O + NAD+ = all-trans-retinoate + 2 H+ + NADH,9-cis-retinal + H2O + NAD+ = 9-cis-retinoate + 2 H+ + NADH,11-cis-retinal + H2O + NAD+ = 11-cis-retinoate + 2 H+ + NADH,13-cis-retinal + H2O + NAD+ = 13-cis-retinoate + 2 H+ + NADH,3-deoxyglucosone + H2O + NAD+ = 2-dehydro-3-deoxy-D-gluconate + 2 H+ + NADH,(E)-4-hydroxynon-2-enal + H2O + NAD+ = (E)-4-hydroxynon-2-enoate + 2 H+ + NADH,H2O + malonaldehyde + NAD+ = 3-oxopropanoate + 2 H+ + NADH,H2O + hexanal + NAD+ = 2 H+ + hexanoate + NADH,H2O + NAD+ + propanal = 2 H+ + NADH + propanoate.acetaldehyde + H2O + NAD+ = acetate + 2 H+ + NADH,benzaldehyde + H2O + NAD+ = benzoate + 2 H+ + NADH,4-aminobutanal + H2O + NAD+ = 4-aminobutanoate + 2 H+ + NADH.

Activity regulation: Inhibited by citral, disulfiram, and cyanamide. Activated by diethylstilbestrol (PubMed:19296407). Inhibited by duocarmycin analogs (PubMed:26373694).

Recommended name: Aldehyde dehydrogenase 1A1

Gene name from HGNC: ALDH1A1 (ALDH1, PUMB1, RALDH1)

HPA class: Enzymes Metabolic proteins Plasma proteins

AlphaFold DB: P00352

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P00352

HPA link: https://www.proteinatlas.org/ENSG00000165092-ALDH1A1

Tissue specificity RNA from HPA: Tissue enhanced (liver)

Tissue expression from HPA: Cytoplasmic expression in selected tissues.

Single cell type specificity Cell type enhanced (Hepatocytes, Respiratory ciliated cells, Leydig cells, Distal tubular cells, Proximal tubular cells)

Immune cell specificity: Immune cell enriched (classical monocyte)

Subcellular summary HPA Located in Cytosol (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in cervical cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000165092-ALDH1A1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000165092-ALDH1A1/pathology/endometrial+cancer

Expression figure legend: ALDH1 is expressed within the basal layer of the endometrium.| ALDH1 is expressed in premalignant endometrium.

Expression figure link: https://www.nature.com/articles/s41598-021-90570-3/figures/3|https://www.nature.com/articles/s41598-021-90570-3/figures/4

Survival figure legend: ALDH expression correlated with survival inTCGA cohort

Survival curve link: https://www.nature.com/articles/s41598-021-90570-3/figures/1

OMIM: 100640

OMIM link2: https://www.omim.org/entry/100640

HGNC ID: HGNC:402

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:402