Proteomic characterization of idiopathic pulmonary fibrosis patients: stable versus acute exacerbation
MONALDI ARCHIVES FOR CHEST DISEASE
Authors: Carleo, Alfonso; Landi, Claudia; Prasse, Antje; Bergantini, Laura; D'Alessandro, Miriana; Cameli, Paolo; Janciauskiene, Sabina; Rottoli, Paola; Bini, Luca; Bargagli, Elena
Abstract
Acute exacerbations (AEs) are among the main causes of death in idiopathic pulmonary fibrosis (IPF) patients. In this study proteomic comparative analysis of bronchoalveolar lavage (BAL) fluid samples was performed in stable IPF patients versus AEs IPF group to identify AE pathogenetic mechanisms and novel potential predictive biomarkers. A functional proteomic analysis of BAL fluid samples from stable and AE-IPF patients was conducted in a population of 27 IPF patients. Fifty-one differentially abundant spots were observed and identified by mass spectrometry. Enrichment analysis found proteins of interest involved in the regulation of macrophages and lipid metabolism receptors. In acute exacerbation IPF group, differentially abundant proteins were involved in propagation of the beta-catenin WNT transduction signal, and proteins up-regulated in lung carcinogenesis (IGKC, S100A9, PEDF, IGHG1, ALDOA, A1AT, HPT, CO3 and PIGR) and acute phase proteins involved in protease-antiprotease imbalance (such as A1AT fragments). Dot-blot analysis of A1AT C-36 peptide allowed validating our fmdings, confirming up-regulation in AF IPF patients and suggesting its potential pathogenetic role. A crucial role of protease/antiprotease imbalance, clathrin-mediated endocytosis signalling and carcinogenesis emerged in IPF patients developing acute exacerbations.
Prognostic implications of the expression levels of different immunoglobulin heavy chain-encoding RNAs in early breast cancer
NPJ BREAST CANCER
Authors: Larsson, Christer; Ehinger, Anna; Winslow, Sofia; Leandersson, Karin; Klintman, Marie; Dahl, Ludvig; Vallon-Christersson, Johan; Hakkinen, Jari; Hegardt, Cecilia; Manjer, Jonas; Saal, Lao; Ryden, Lisa; Malmberg, Martin; Borg, Ake; Loman, Niklas
Abstract
The extent and composition of the immune response in a breast cancer is one important prognostic factor for the disease. The aim of the current work was to refine the analysis of the humoral component of an immune response in breast tumors by quantifying mRNA expression of different immunoglobulin classes and study their association with prognosis. We used RNA-Seq data from two local population-based breast cancer cohorts to determine the expression of IGJ and immunoglobulin heavy (IGH) chain-encoding RNAs. The association with prognosis was investigated and public data sets were used to corroborate the findings. Except for IGHE and IGHD, mRNAs encoding heavy chains were generally detected at substantial levels and correlated with other immune-related genes. High IGHGT mRNA was associated with factors related to poor prognosis such as estrogen receptor negativity, HER2 amplification, and high grade, whereas high IGHA2 mRNA levels were primarily associated with lower age at diagnosis. High IGHA2 and IGJ mRNA levels were associated with a more favorable prognosis both in univariable and multivariable Cox models. When adjusting for other prognostic factors, high IGHG1 mRNA levels were positively associated with improved prognosis. To our knowledge, these results are the first to demonstrate that expression of individual Ig class types has prognostic implications in breast cancer.