Biomarker: CD44

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/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: Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:19703720, PubMed:22726066). Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection (PubMed:7528188). Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:18757307, PubMed:23589287). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (PubMed:15123640).

UniProt ID: P16070

UniProt Link: https://www.uniprot.org/uniprotkb/P16070/entry

Biological function from UniProt: #Cell adhesion

Molecular function from UniProt:

Tissue specificity from UniProt: Isoform 10 (epithelial isoform) is expressed by cells of epithelium and highly expressed by carcinomas. Expression is repressed in neuroblastoma cells.

Subcellular UniProt: #Cell membrane #Cell projection #Membrane

Alternative name from UniProt:

Recommended name: CD44 antigen

Gene name from HGNC: CD44 (CD44R, CSPG8, HCELL, IN, MC56, MDU2, MDU3, MIC4, Pgp1)

CD antigen name: CD44

HPA class: Blood group antigen proteins Cancer-related genes CD markers FDA approved drug targets Plasma proteins

AlphaFold DB: P16070

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P16070

Developmental stage: Expressed in the developing retina between 16 and 19 weeks post-conception, specifically in the outer neuroblastic zone, inner neuroblastic zone, interphotoreceptor zone and the retinal pigment epithelium (at protein level).

HPA link: https://www.proteinatlas.org/ENSG00000026508-CD44

Tissue specificity RNA from HPA: Tissue enhanced (salivary gland)

Tissue expression from HPA: Cytoplasmic and membranous expression in most epithelial and lymphoid tissues.

Single cell type specificity Cell type enhanced (Langerhans cells, Suprabasal keratinocytes, Basal keratinocytes, Ductal cells, Exocrine glandular cells)

Immune cell specificity: Low immune cell specificity

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000026508-CD44/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000026508-CD44/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

Note2: A number sign (#) is used with this entry because the Indian blood group antigens result from a polymorphism in the CD44 gene

OMIM: 107269;172290;

OMIM link2: https://www.omim.org/entry/107269;https://www.omim.org/entry/172290;

Phenotype: 609027;BLOOD GROUP, INDIAN SYSTEM; IN

HGNC ID: HGNC:1681

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1681