Biomarker: CXCL12

Histology type: endometrial carcinoma

Country: USA

Region: Rockville

Followed up time :

Subgroup 1 name : Negative

Subgroup 1 number: 71

Subgroup 2 name: Positive

Subgroup 2 number: 129

Conclusion: Positive CXCL12 expression was associated with longer overall survival (OS) (log-rank p = 0.006) and longer recurrence-free survival (RFS) (log-rank p = 0.01) in ER negative patients, but not in ER positive patients. We identified a unique molecular signature associated with better OS and RFS in EC patients. In addition to pathological characteristics of the tumor, expression of CXCL12 and ER may be clinically useful for assigning adjuvant treatment to EC cases.

Sample type : tissue

Sample method: immunohistochemisty

Expression pattern : expression

Expression elevation: A case was considered to have positive expression when any cells showed positive staining. Furthermore, tumor and stromal localization was analyzed from a single slide. Cytoplasmic and membranous staining for CXCL12. Although expression was observed in several compartments, our evaluation of CXCL12 staining was an overall assessment, not a cellular compartment-specific assessment. Stromal expression of CXCL12 was absent in all cases.

Statictics: cutoff<65;cutoff>65

Cohort age: 109;90

Subgroup 1 age: 27;44

Subgroup 2 age: 73;56

Funtion Uniprot: Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (By similarity)

UniProt ID: P48061

UniProt Link: https://www.uniprot.org/uniprotkb/P48061/entry

Biological function from UniProt: #Chemotaxis #Host-virus interaction

Molecular function from UniProt:

Tissue specificity from UniProt: Isoform Alpha and isoform Beta are ubiquitously expressed, with highest levels detected in liver, pancreas and spleen. Isoform Gamma is mainly expressed in heart, with weak expression detected in several other tissues. Isoform Delta, isoform Epsilon and isoform Theta have highest expression levels in pancreas, with lower levels detected in heart, kidney, liver and spleen.

Subcellular UniProt: #Secreted

Alternative name from UniProt:

Cleaved: Cleaved into 2 chains SDF-1-beta(3-72) SDF-1-alpha(3-67)

Recommended name: Stromal cell-derived factor 1

Gene name from HGNC: CXCL12 (PBSF, SCYB12, SDF-1a, SDF-1b, SDF1, SDF1A, SDF1B, TLSF-a, TLSF-b, TPAR1)

HPA class: Secreted

AlphaFold DB: P48061

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P48061

Developmental stage: Isoform Alpha is ubiquitously expressed in fetal tissues. Isoform Beta and isoform Delta have more limited expression patterns, with highest levels detected in fetal spleen and fetal liver, respectively. Isoform Gamma and isoform Theta are weakly detected in fetal kidney.

HPA link: https://www.proteinatlas.org/ENSG00000107562-CXCL12

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Cytoplasmic and nuclear expression in most tissues with additional plasma positivity.

Single cell type specificity Cell type enhanced (Fibroblasts, Adipocytes, Kupffer cells, Distal tubular cells, Smooth muscle cells)

Immune cell specificity: Not detected in immune cells

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000107562-CXCL12/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000107562-CXCL12/pathology/endometrial+cancer

Expression figure legend: IHC stains for CXCL12 expression

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291748/figure/F1/

Survival figure legend: The association between CXCL12 expression and survival outcomes differed by ER expression status.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291748/figure/F2/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291748/figure/F3/

OMIM: 600835

OMIM link2: https://www.omim.org/entry/600835

HGNC ID: HGNC:10672

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10672