Biomarker: ALDH1

Histology type: endometrial carcinoma

Country: Italy

Region: Bari

Study type: prospective

Followed up time :

Subgroup 1 name : <Both expression score median

Subgroup 1 number: 36

Subgroup 2 name: >Both expression score

Subgroup 2 number: 18

Conclusion: The combination of ALDH1 and CD44 could be a promising marker for developing additional targeted therapy for severe endometrial cancers.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : ALDH1 High（>10）/CD44+

Expression elevation: The ALDH1 and CD44 intensity of individual tumor cells was scored as 0 (no staining), 1+ (weak intensity), 2+ (moderate intensity), or 3+ (strongest intensity). The percentages of cells with ALDH1 and CD44 staining at each intensity were also estimated (range, 0–100). For the semiquantitative analysis of the ALDH1 and CD44 production, the absolute ALDH1 and CD44 scores were calculated by multiplying the estimated percentages of stained cells at each intensity by the corresponding intensity value, which produced immunostaining scores ranging from 0–300.To compare the absolute ALDH1 and CD44 scores between different endometrial lesions, the optimal cut-off values of the ALDH1 and CD44 f-scores were determined using receiver operating characteristic curve analysis. ALDH1Low was defined as a score below 10, and ALDH1 High was defined as a score higher than 10. CD44- was defined as a score of 0, and CD44+ was defined as a score higher than 0.

Statictics: Mean (SD)

Cohort age: 52.72±1.67

Subgroup 1 age: 52.72±1.67

Subgroup 2 age: 58.89±3.63

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: Examples of immunohistochemical staining for ALDH1 in endometrial lesions.$ Examples of immunohistochemical staining for CD44 in endometrial lesions.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205661/figure/pone.0206685.g001/?report=objectonly$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205661/figure/pone.0206685.g002/?report=objectonly

Survival figure legend: Kaplan–Meier analysis of survival in patients with EC based on ALDH1 and CD44 protein immunostaining.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205661/figure/pone.0206685.g003/?report=objectonly

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