Identification of LCN1 as a Potential Biomarker for Breast Cancer by Bioinformatic Analysis.

The biological functions of lipocalin-1 (LCN1) are involved in innate immune responses and act as a physiological scavenger of potentially harmful lipophilic molecules. However, the relevance of LCN1 with cancer is rarely concerned currently. The aim of this study is to address the relevance of LCN1 with BRCA by bioinformatics. In this study, we found that the expressions of LCN1 increased significantly in various cancerous tissues, including BRCA, compared with their adjacent normal tissues through the TIMER database. Furthermore, UALCAN database analysis showed that the expression of LCN1 increased gradually from stage 1 to stage 4 and was upregulated in BRCA patients with different races and subtypes compared with that in the normal. In addition, those patients with perimenopause and postmenopause status displayed higher LCN1 expression. Importantly, LCN1 genetic alterations, including copy number amplification, deep deletion, and missense mutation, could be found, and the alteration frequency showed difference in various invasive BRCA through cBioPortal database. Moreover, a positive correlation between LCN1 somatic copy number alterations and immune cell enrichments was revealed in basal like BRCA by GISTIC 2.0. Finally, analysis on prognostic value of LCN1 by Kaplan-Meier plotter showed that low LCN1 expression correlated with poor prognosis for relapse-free survival in all types of BRCA, overall survival in luminal B BRCA, distant metastasis free survival in human epithelial growth factor receptor-2 (HER2) positive BRCA, and postprogression survival (PPS) in luminal A BRCA. But high LCN1 expression also displayed poor prognosis for PPS in HER2 positive BRCA. The results together verified the significance of LCN1 in BRCA, suggesting that it may be a potential biomarker for BRCA diagnosis.

Human CD4+ T cell responses to the dog major allergen Can f 1 and its human homologue tear lipocalin resemble each other.

Lipocalin allergens form a notable group of proteins, as they contain most of the significant respiratory allergens from mammals. The basis for the allergenic capacity of allergens in the lipocalin family, that is, the development of T-helper type 2 immunity against them, is still unresolved. As immunogenicity has been proposed to be a decisive feature of allergens, the purpose of this work was to examine human CD4+ T cell responses to the major dog allergen Can f 1 and to compare them with those to its human homologue, tear lipocalin (TL). For this, specific T cell lines were induced in vitro from the peripheral blood mononuclear cells of Can f 1-allergic and healthy dog dust-exposed subjects with peptides containing the immunodominant T cell epitopes of Can f 1 and the corresponding TL peptides. We found that the frequency of Can f 1 and TL-specific T cells in both subject groups was low and close to each other, the difference being about two-fold. Importantly, we found that the proliferative responses of both Can f 1 and TL-specific T cell lines from allergic subjects were stronger than those from healthy subjects, but that the strength of the responses within the subject groups did not differ between these two antigens. Moreover, the phenotype of the Can f 1 and TL-specific T cell lines, determined by cytokine production and expression of cell surface markers, resembled each other. The HLA system appeared to have a minimal role in explaining the allergenicity of Can f 1, as the allergic and healthy subjects' HLA background did not differ, and HLA binding was very similar between Can f 1 and TL peptides. Along with existing data on lipocalin allergens, we conclude that strong antigenicity is not decisive for the allergenicity of Can f 1.

Two newly identified cat allergens: the von Ebner gland protein Fel d 7 and the latherin-like protein Fel d 8.

INTRODUCTION: Characterization of the complete IgE binding spectrum of cat allergens is important for the development of improved diagnosis and effective immunotherapeutics. While Fel d 1 remains unchallenged as the major cat allergen, we now report the isolation of two new allergens capable of binding similar concentrations of IgE in the allergic sera of some individuals. MATERIALS AND METHODS: Cat tongue and submandibular salivary gland cDNA libraries were screened by DNA hybridisation and IgE immunoassay. The isolated DNA fragments were sub-cloned into an E. coli expression system and the IgE reactivity was examined with human cat-allergic sera using a DELFIA IgE quantitation assay. RESULTS: Fel d 7, an 18 kDa von Ebner gland protein Can f 1 homologue, was isolated from the tongue library. Fel d 8, a 24-kDa latherin-like protein with homology to Equ c 5, was isolated from the submandibular library. The frequency of IgE binding of cat-allergic sera to recombinant Fel d 1, 7 and 8 was 60.5, 37.6 and 19.3%, respectively. Inhibition studies indicated some IgE binding cross-reactivity between Fel d 7 and dog dander extracts. DISCUSSION: The study reports the isolation and characterization of two new cat allergens. The isolation of these allergens provides the opportunity to determine the role that IgE binding proteins other than Fel d 1 play in cat-allergic disease. For cat-allergic individuals with moderate to mild rhinoconjunctivitis these allergens may play a more important role in the manifestation of their allergic disease.

Antibodies to endogenous tear protein in normal human tears.

PURPOSE: To identify endogenous tear proteins immunoselected by antibodies from normal human ocular tears. MATERIALS AND METHODS: Proteins were immunoselected from normal human tear samples without the addition of primary antibodies. Captured proteins were electrophoresed in polyacrylamide gels and silver stained. Human tears were also used as primary antibodies on immunoblots of tear proteins. RESULTS: Lysozyme, lipocalin-1, and lactoferrin were immunoselected from normal human tear samples without the addition of primary antibodies. Antibodies from normal tears recognized lysozyme on immunoblots of tear proteins. CONCLUSION: Normal human ocular tears contain antibodies to endogenous tear protein.

Animal-derived lipocalin allergens exhibit immunoglobulin E cross-reactivity.

BACKGROUND: Although knowledge of the IgE cross-reactivity between allergens is important for understanding the mechanisms of allergy, the regulation of the allergic immune response and the development of efficient modes of allergen immunotherapy, the cross-reactivity of animal allergens is poorly known. OBJECTIVE: The aim of this study was to characterize IgE cross-reactivities between lipocalin proteins, including five animal-derived lipocalin allergens and one human endogenous lipocalin, tear lipocalin (TL). METHODS: The recombinant proteins were validated by chromatography and mass spectrometry. The IgE-binding capacity of the allergens was confirmed by IgE. immunoblotting and IgE immunoblot inhibition. IgE ELISA was performed with sera from 42 atopic patients and 21 control subjects. The IgE cross-reactivities between the lipocalin proteins were determined by ELISA inhibition. RESULTS: ELISA inhibition revealed IgE cross-reactivities between Can f 1 and human TL, between Can f 1 and Can f 2, and between Equ c 1 and Mus m 1. Low levels of IgE to human TL were found in the sera of seven dog-allergic patients of whom six were IgE-positive for Can f 1. CONCLUSION: Several lipocalins exhibited IgE cross-reactivity, probably due to the sequential identity of the proteins and also due to similarities in their three-dimensional structures. The clinical significance of the findings needs to be elucidated. Low-level IgE cross-reactivity can play a role in regulating immune response to lipocalin allergens.