Biomarker: Lactoferrin (Lf)

Histology type: endometrial carcinoma

Country: Italy

Region: Messina

Followed up time :

Subgroup 1 name : positive

Subgroup 1 number: 43

Subgroup 2 name: negative

Subgroup 2 number: 28

Conclusion: Survival analysis in EC indicated the architectural, nuclear and combined histologic grades as well as the stage, PR, Ki-67 and NORA as significant parameters. The utilization of Lf as a prognostic marker, able to identify patients at different risk of death, or alternatively, its clinical application as therapeutic agent, must be considered with great caution.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : higher Lf ID-score

Funtion Uniprot: Transferrins are iron binding transport proteins which can bind two Fe3+ ions in association with the binding of an anion, usually bicarbonate.1 Publication Lactotransferrin Major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions (PubMed:14573629, PubMed:1599934, PubMed:6802759, PubMed:3169987, PubMed:11179314, PubMed:12693969). Has antimicrobial activity, which depends on the extracellular cation concentration (PubMed:6802759). Antimicrobial properties include bacteriostasis, which is related to its ability to sequester free iron and thus inhibit microbial growth, as well as direct bactericidal properties leading to the release of lipopolysaccharides from the bacterial outer membrane (PubMed:14573629, PubMed:1599934, PubMed:6802759, PubMed:3169987, PubMed:11179314, PubMed:12693969). Can also prevent bacterial biofilm development in P.aeruginosa infection (PubMed:12037568). Has weak antifungal activity against C.albicans (PubMed:11083624). Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth (PubMed:15166119). Promotes binding of species C adenoviruses to epithelial cells, promoting adenovirus infection (PubMed:17079302). Can inhibit papillomavirus infections (PubMed:17481742). Stimulates the TLR4 signaling pathway leading to NF-kappa-B activation and subsequent pro-inflammatory cytokine production while also interfering with the lipopolysaccharide (LPS)-stimulated TLR4 signaling (PubMed:20345905). Inhibits neutrophil granulocyte migration to sites of apoptosis, when secreted by apoptotic cells (PubMed:19033648). Stimulates VEGFA-mediated endothelial cell migration and proliferation (PubMed:16842782). Binds heparin, chondroitin sulfate and possibly other glycosaminoglycans (GAGs) (PubMed:9359845). Also binds specifically to pneumococcal surface protein A (PspA), the lipid A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA (PubMed:9359845).15 Publications Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection (PubMed:17481742). N-terminal region shows strong antifungal activity against C.albicans (PubMed:11083624). Contains two BBXB heparin-binding consensus sequences that appear to form the predominate functional GAG-binding site2 Publications Kaliocin-1 Has antimicrobial activity and is able to permeabilize different ions through liposomal membranes.1 Publication Lactoferroxin-A Has opioid antagonist activity (PubMed:1369293). Shows preference for mu-receptor (PubMed:1369293).1 Publication Lactoferroxin-B Has opioid antagonist activity (PubMed:1369293). Shows higher degrees of preference for kappa-receptors than for mu-receptors (PubMed:1369293).1 Publication Lactoferroxin-C Has opioid antagonist activity (PubMed:1369293). Shows higher degrees of preference for kappa-receptors than for mu-receptors (PubMed:1369293).1 Publication The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions (PubMed:12535064). This function contributes to the antimicrobial activity (PubMed:12535064). Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites (PubMed:12535064).1 Publication Isoform DeltaLf Transcription factor with antiproliferative properties and ability to induce cell cycle arrest (PubMed:15222485). Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELENOH promoters (PubMed:22320386).2 Publications

UniProt ID: P02788

UniProt Link: https://www.uniprot.org/uniprotkb/P02788/entry

Biological function from UniProt: #Immunity #Ion transport #Iron transport #Osteogenesis #Transcription

Molecular function from UniProt:

Tissue specificity from UniProt: High levels are found in saliva and tears, intermediate levels in serum and plasma, and low levels in urine. In kidney, detected in the distal collecting tubules in the medulla but not in the cortical region or in blood vessels. Detected in peripheral blood neutrophils (at protein level). Isoform 1 and isoform DeltaLf are expressed in breast, prostate, spleen, pancreas, kidney, small intestine, lung, skeletal muscle, uterus, thymus and fetal liver. Isoform 1 is expressed in brain, testis and peripheral blood leukocytes; isoform DeltaLf is barely detectable in these tissues. Isoform DeltaLf is expressed in placenta, liver and ovary; isoform 1 is barely detectable in these tissues. In kidney, isoform 1 is expressed at high levels in the collecting tubules of the medulla but at very low levels in the cortex.

Subcellular UniProt: #Cytoplasm #Nucleus #Secreted

Alternative name from UniProt:

Cleaved: Lactoferricin-H (Lfcin-H) Kaliocin-1 Lactoferroxin-A Lactoferroxin-B Lactoferroxin-C

Recommended name: Lactotransferrin

Gene name from HGNC: LTF (HLF2)

HPA class: Cancer-related genes Plasma proteins

AlphaFold DB: P02788

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P02788

HPA link: https://www.uniprot.org/uniprotkb/P02788/entry

Tissue specificity RNA from HPA: Group enriched (bone marrow, salivary gland)

Tissue expression from HPA: Cytoplasmic expression with additional secreted positivity in several tissues including salivary gland, bone marrow, prostate and lactating breast.

Single cell type specificity Cell type enriched (Breast glandular cells)

Immune cell specificity: Group enriched (non-classical monocyte, neutrophil)

Cancer prognostic summary HPA Prognostic marker in renal cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000012223-LTF/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000012223-LTF/pathology/endometrial+cancer

OMIM: 150210

OMIM link2: https://www.omim.org/entry/150210

HGNC ID: HGNC:6720

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6720