Biomarker: Ki-67 nuclear antigen labeling

Histology type: endometrial carcinoma

Country: Japan

Region: Tokyo

Study type: prospective study

Followed up time :

Conclusion: In conclusion, a higher epithelial cell size ratio after 4 weeks of treatment in conjunction with lower Ki-67 nuclear antigen labeling indices could be a potential predictor of hormonal response.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : higher epithelial cell size ratio after 4 weeks + lower Ki-67 nuclear antigen labeling

Expression elevation: Finally the labeling index for Ki-67 could be calculated on the basis of the number of positive cells as a percentage of the total number of both positive cells and negative cells, and the resulting indices obtained during the pretreatment to posttreatment periods were compared between good responders and poor responders.

Funtion Uniprot: Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). Associates with the surface of the mitotic chromosome, the perichromosomal layer, and covers a substantial fraction of the chromosome surface (PubMed:27362226). Prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization (PubMed:24867636). It is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in maintaining mitotic chromosomes dispersed (Probable)

UniProt ID: P46013

UniProt Link: https://www.uniprot.org/uniprotkb/P46013/entry

Biological function from UniProt: #Cell cycle

Molecular function from UniProt:

Subcellular UniProt: #Chromosome #Nucleus

Alternative name from UniProt:

Caution: Was thought to play a key role in cell proliferation, and is commonly used as a marker of cell proliferation (PubMed:6339421, PubMed:21960707). However, its primary function is uncoupled from cell proliferation: it is required to maintain mitotic chromosomes dispersed by forming a steric and electrostatic charge barrier (PubMed:27362226).

Miscellaneous: Biotechnology Widely used as a marker to assess cell proliferation, as it is detected in the nucleus of proliferating cells only (PubMed:6339421, PubMed:21960707). In cancer research field for example, MKI67 is the most widely used marker for comparing proliferation between tumor samples (PubMed:21960707, PubMed:26680267).

Recommended name: Proliferation marker protein Ki-67

Gene name from HGNC: MKI67 (MIB-1, PPP1R105)

HPA class: Cancer-related genes Plasma proteins

AlphaFold DB: 5j28

AlphaFold Link: https://www.ebi.ac.uk/pdbe/entry/pdb/5J28

Developmental stage: Expression occurs preferentially during late G1, S, G2 and M phases of the cell cycle, while in cells in G0 phase the antigen cannot be detected (at protein level) (PubMed:6206131). Present at highest level in G2 phase and during mitosis (at protein level). In interphase, forms fiber-like structures in fibrillarin-deficient regions surrounding nucleoli (PubMed:2674163, PubMed:8799815).

HPA link: https://www.proteinatlas.org/ENSG00000148773-MKI67

Tissue specificity RNA from HPA: Group enriched (bone marrow, lymphoid tissue)

Tissue expression from HPA: Nuclear expression most abundant in germinal center cells and in a subset of cells in several tissues including squamous epithelia, cells in seminiferous ducts and the gastrointestinal tract.

Single cell type specificity Cell type enhanced (Erythroid cells, Plasma cells, Granulosa cells, Extravillous trophoblasts)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Nucleoli rim, Mitotic chromosome (Single cell variability, CCD Protein, CCD Transcript)

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), liver cancer (unfavorable) and pancreatic cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000148773-MKI67/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000148773-MKI67/pathology/endometrial+cancer

OMIM: 176741

OMIM link2: https://www.omim.org/entry/176741

HGNC ID: HGNC:7107

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7107