Biomarker: Indoleamine 2,3-dioxygenase

Histology type: endometrial carcinoma

Country: Japan

Region: Obu

Followed up time :

Subgroup 1 name : High IDO expression(IDO2 + or 3 + )

Subgroup 1 number: 37

Subgroup 2 name: Low expression

Subgroup 2 number: 43

Conclusion: These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.

Sample type : tissue

Sample method: Immunohistochemistry

Expression pattern : high IDO expression

Expression elevation: The IDO expression levels were classified semiquantitatively based on the total scores of the percent positivity of stained tumour cells and the staining intensity. Namely, the percent positivity was scored as ‘0’ if <5% (negative), ‘1’ if 5–30% (sporadic), ‘2’ if 30–70% (focal), and ‘3’ if >70% (diffuse) of cells stained, whereas the staining intensity was scored relative to the known positive and negative controls as ‘0’ if no staining, ‘1’ if weakly stained, ‘2’ if moderately stained (intermediate level between strong and weak), and ‘3’ if strongly stained. The final IDO expression score was defined as follows; ‘IDO−’ if the sum of the percent positivity score and the staining intensity score was 0–1, ‘IDO1+’ if the sum was 2–3, ‘IDO2+’ if the sum was 4–5, and ‘IDO3+’ if the sum was 6.

Funtion Uniprot: Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses (PubMed:25691885). Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells (PubMed:25691885). Acts as a suppressor of anti-tumor immunity (PubMed:23103127, PubMed:25157255, PubMed:14502282, PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan (PubMed:25691885). Protects the fetus from maternal immune rejection (PubMed:25691885).

UniProt ID: P14902

UniProt Link: https://www.uniprot.org/uniprotkb/P14902/entry

Biological function from UniProt: Immunity, Tryptophan catabolism

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in mature dendritic cells located in lymphoid organs (including lymph nodes, spleen, tonsils, Peyers's patches, the gut lamina propria, and the thymic medulla), in some epithelial cells of the female genital tract, as well as in endothelial cells of term placenta and in lung parenchyma (PubMed:25691885). Weakly or not expressed in most normal tissues, but mostly inducible in most tissues (PubMed:25691885). Expressed in more than 50% of tumors, either by tumoral, stromal, or endothelial cells (expression in tumor is associated with a worse clinical outcome) (PubMed:18418598). Not overexpressed in tumor-draining lymph nodes (PubMed:26155395, PubMed:25691885)

Subcellular UniProt: #Cytoplasm

Alternative name from UniProt:

Miscellaneous: IDO1 is the target for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation.1 Publication IDO1 and IDO2 are 2 distinct enzymes which catalyze the same reaction. IDO2 affinity for tryptophan is much lower than that of IDO1. 50% of Caucasians harbor polymorphisms which abolish IDO2 enzymatic activity. IDO2 is expressed in human tumors in an inactive form: tryptophan degradation is entirely provided by IDO1 in these cells (PubMed:18418598). IDO2 may play a role as a negative regulator of IDO1 by competing for heme-binding with IDO1 (PubMed:25394548). Low efficiency IDO2 enzymes have been conserved throughout vertebrate evolution, whereas higher efficiency IDO1 enzymes are dispensable in many lower vertebrate lineages (PubMed:25950090). IDO1 may have arisen by gene duplication of a more ancient proto-IDO gene before the divergence of marsupial and eutherian (placental) mammals3 Publications Elevated IDO1 expression is a hallmark of major viral infections including HIV, HBV, HCV or influenza and also of major bacteria infections, such as Tb, CAP, listeriosis and sepsis. Depletion of tryptophan and production of tryptophan metabolites with bactericidal activity are important as direct anti-pathogen mechanisms. Pathogens are able to highjack the immunosuppressive effects of IDO1 and make use of them to facilitate their own life cycle.

Gene name from HGNC: IDO1 (IDO, INDO)

HPA class: Cancer-related genes Enzymes Metabolic proteins

AlphaFold DB: P14902

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P14902

HPA link: https://www.proteinatlas.org/ENSG00000131203-IDO1

Tissue specificity RNA from HPA: Tissue enhanced (lymphoid tissue, placenta)

Tissue expression from HPA: High cytoplasmic expression in lymphoid cells and placental endothelial cells.

Single cell type specificity Cell type enriched (monocytes)

Immune cell specificity: Immune cell enriched (eosinophil)

Subcellular summary HPA Located in Nucleoplasm, Vesicles, Mitochondria, Cytosol (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), ovarian cancer (favorable) and melanoma (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000131203-IDO1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000131203-IDO1/pathology/endometrial+cancer

Expression figure legend: Representative immunohistochemical staining for IDO expression in endometrial cancer tissues.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360726/#!po=38.8889

Survival figure legend: Overall survival and PFS curves drawn using the Kaplan–Meier method according to the IDO expression in endometrial cancer patients

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360726/figure/fig3/?report=objectonly

OMIM: 147435

OMIM link2: https://www.omim.org/entry/147435

HGNC ID: HGNC:6059

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6059;https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:27269;