Biomarker: clusterin

Histology type: endometrial carcinoma

Stage: early stage

Country: Arabia

Region: Saudi

Study type: retrospective study

Followed up time :

Subgroup 1 name : EC

Subgroup 1 number: 71

Subgroup 2 name: non-cancerous endometrium

Subgroup 2 number: 30

Conclusion: The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : expression

Expression elevation: The immunostaining was measured for both intensity and the frequency of positive cells. First, the frequency of positive cells was measured semi quantitatively in three 40x fields, if the three fields showed positive immunoreactivity in more than 5% of tumor cells, immunostaining was considered positive. Second, the positive cases for clusterin immunostaining were scored for intensity of stain by two pathologists using scoring system of Al-Maghrabi et al., i.e., weak staining +1, moderate +2, and strong +3. The score of staining intensity was accounted in the final score.

Funtion Uniprot: Isoform 1 Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17412999, PubMed:17407782). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement (PubMed:2780565). Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity).By Similarity17 Publications Isoform 6 Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity.1 Publication Isoform 4 Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Promotes cell death through interaction with BCL2L1 that releases and activates BAX (PubMed:21567405).

UniProt ID: P10909

UniProt Link: https://www.uniprot.org/uniprotkb/P10909/entry

Biological function from UniProt: Apoptosis, Complement pathway, Immunity, Innate immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Detected in blood plasma, cerebrospinal fluid, milk, seminal plasma and colon mucosa. Detected in the germinal center of colon lymphoid nodules and in colon parasympathetic ganglia of the Auerbach plexus (at protein level). Ubiquitous. Detected in brain, testis, ovary, liver and pancreas, and at lower levels in kidney, heart, spleen and lung.

Subcellular UniProt: #Cytoplasm #Cytoplasmic vesicle #Endoplasmic reticulum #Membrane #Microsome

Alternative name from UniProt:

Caution: Isoform 4 has been previously detected in cytosol and in the nuclei of apoptotic cells and promoted apoptosis following irradiation (PubMed:12551933). However the nuclear localization and apoptosis promotion has not been confirmed in other cell types (PubMed:24073260).

Cleaved: Clusterin beta chain Alternative names: ApoJalphaComplement cytolysis inhibitor a chain Clusterin alpha chain Alternative names: ApoJbetaComplement cytolysis inhibitor b chain

Recommended name: Clusterin

Gene name from HGNC: CLU (APOJ, CLI, CLU1, CLU2, KUB1, SGP-2, SP-40, TRPM-2)

HPA class: Cancer-related genes Candidate cardiovascular disease genes Plasma proteins

AlphaFold DB: P10909

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P10909

Induction: Up-regulated in response to enterovirus 71 (EV71) infection (at protein level) (PubMed:16548883). Up-regulated by agents that induce apoptosis, both at mRNA and protein level (PubMed:17689225). Isoform 1 is up-regulated by androgen (PubMed:17148459). Isoform 2 is down-regulated by androgen (PubMed:17148459).

HPA link: https://www.proteinatlas.org/ENSG00000120885-CLU

Tissue specificity RNA from HPA: Tissue enhanced (brain, liver)

Tissue expression from HPA: Selective cytoplasmic expression in islet cells in pancreas, squamous epithelia in tonsil, glandular cells in cervix, uterus and epididymis.

Single cell type specificity Group enriched (Muller glia cells, Hepatocytes, Collecting duct cells, Cholangiocytes)

Immune cell specificity: Immune cell enriched (basophil)

Subcellular summary HPA Located in Cytosol

Cancer prognostic summary HPA Prognostic marker in thyroid cancer (favorable) .

Pathology link: https://www.proteinatlas.org/ENSG00000120885-CLU/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000120885-CLU/pathology/endometrial+cancer

OMIM: 185430

OMIM link2: https://www.omim.org/entry/185430

HGNC ID: HGNC:2095

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2095