Biomarker: PD-L1

Histology type: endometrial carcinoma

Stage: advanced stage

Region: Minia

Followed up time :

Subgroup 1 name : negative

Subgroup 1 number: 219

Subgroup 2 name: positive

Subgroup 2 number: 93

Conclusion: PD-L1 is promising potential prognostic biomarkers in endometrial carcinomas since their overexpression is associated with clinicopathologic variables of advanced disease.PD-L1 and HIF-1α proteins are promising potential prognostic biomarkers in endometrial carcinomas since their overexpression is associated with clinicopathologic variables of advanced disease.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : overexpression ( total score was ≥3)

Expression elevation: Positive immunostaining of PD-L1 was membranous, and HIF-1α was nuclear. Positive cases were classified according to the rate (percentage) of positive cell staining (R) on the one hand and their staining intensity (I) on the other hand. Immunostaining of <10% of tumor cells is categorized as 0, immunostaining of 10%–25% of tumor cells as 1, staining of 26%–50% of tumor cells as 2, staining of 51%–75% as 3, and staining of >75% as 4. The staining intensity in each specimen was categorized as 1, 2, and 3 (weak, moderate, or strong, respectively). The total immunostaining score (I × R) was assigned to each case by multiplying the score for the percentage of positive tumor cells (1–4) by staining intensity score (1–3) resulting in a total score of 1–12. For statistical purposes, the investigated cases were categorized as negative if the total score was <3 and positive if the total score was ≥3.

Statictics: Mean (SD);Range

Cohort age: 63.4;27-89

Subgroup 1 age: 63.0;27-89

Subgroup 2 age: 64.4;44-83

Funtion Uniprot: Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813417, PubMed:28813410). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813417, PubMed:28813410). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077).4 Publications The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28813417, PubMed:28813410). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (By similarity).

UniProt ID: Q9NZQ7

UniProt Link: https://www.uniprot.org/uniprotkb/Q9NZQ7/entry

Biological function from UniProt: Adaptive immunity, Immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes

Subcellular UniProt: #Cell membrane #Endosome #Membrane

Alternative name from UniProt:

Recommended name: Programmed cell death 1 ligand 1

Gene name from HGNC: CD274 (B7-H, B7-H1, B7H1, PD-L1, PDCD1LG1, PDL1)

HPA class: Cancer-related genes CD markers Disease related genes FDA approved drug targets

AlphaFold DB: Q9NZQ7

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q9NZQ7

Induction: Up-regulated on T- and B-cells, dendritic cells, keratinocytes and monocytes after LPS and IFNG activation. Up-regulated in B-cells activated by surface Ig cross-linking.

HPA link: https://www.proteinatlas.org/ENSG00000120217-CD274

Tissue specificity RNA from HPA: Tissue enhanced (lung)

Tissue expression from HPA: High expression in placental trophoblasts.

Single cell type specificity Cell type enhanced (Langerhans cells, Syncytiotrophoblasts, monocytes, granulocytes, Extravillous trophoblasts)

Immune cell specificity: Immune cell enhanced (basophil)

Subcellular summary HPA Located in Nucleoplasm, Plasma membrane, Actin filaments

Cancer prognostic summary HPA Prognostic marker in colorectal cancer (favorable) and breast cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000120217-CD274/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000120217-CD274/pathology/endometrial+cancer

Disease: No disease ID

Note1: Truncation of the 3'-untranslated (3'-UTR) region of CD274 transcripts leads to elevated expression of CD274 in multiple cancers including T-cell leukemia, diffuse large B-cell lymphoma and stomach adenocarcinoma (PubMed:27281199). Disruption of 3'-UTR region is caused by structural variants that stabilize CD274 transcripts, leading to overexpression (PubMed:27281199). Increased expression in tumors promotes immune evasion and tumor cell growth by allowing malignant cells to escape destruction by the immune system (PubMed:27281199)

OMIM: 605402

OMIM link2: https://www.omim.org/entry/605402

HGNC ID: HGNC:17635

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17635