Dataset Information

BAL proteomic signature of lung adenocarcinoma in IPF patients and its transposition in serum samples for less invasive diagnostic procedures

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a form of chronic and irreversible fibrosing interstitial pneumonia of unknown aetiology, with an average survival time of 3-5 years after diagnosis. Emerging evidence suggests that IPF increases the risk of lung carcinogenesis. Both diseases show similarities in terms of risk factors, such as history of smoking, concomitant emphysema, and viral infections, besides sharing similar pathogenic pathways. Lung cancer diagnosis is often difficult in IPF patients because of the diffuse lung injuries and abnormalities due to the underlying fibrosis. This is reflected in the lack of optimal therapeutic strategies for patients with both diseases. For this purpose, we performed a proteomic study on bronchoalveolar lavage (BAL) samples from IPF, LC associated with IPF (LC-IPF) patients, and healthy controls (CTRL). Molecular pathways involved in inflammation, immune response, lipid metabolism and cell adhesion were found for the dysregulated proteins in LC-IPF, of which TTHY, APOA1, S10A9, RET4, GDRI1 and PROF1. The correlation test revealed a relationship between inflammation-related proteins and proteins associated with lipid metabolism. Also, the up-regulation of PROF1 in LC-IPF BAL and S10A9 in LC-IPF serum was validated. While APOA1 and APOE were validated as highly abundant in IPF BAL and low abundant in IPF serum. We evaluated nicotinamide phosphoribosyltransferase levels in serum highlighting its down-regulation in LC-IPF. Our retrospective analyses on BAL of IPF and LC-IPF patients extrapolate some potential biomarkers whose further evaluation at the serum level, permits the measurement of these potential biomarkers with a less invasive procedure.

INSTRUMENT(S): ultraflex

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bronchoalveolar Lavage

SUBMITTER: Lorenza Vantaggiato

LAB HEAD: Luca Bini

PROVIDER: PXD037720 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications

BAL Proteomic Signature of Lung Adenocarcinoma in IPF Patients and Its Transposition in Serum Samples for Less Invasive Diagnostic Procedures.

Vantaggiato Lorenza L Shaba Enxhi E Cameli Paolo P Bergantini Laura L d'Alessandro Miriana M Carleo Alfonso A Montuori Giusy G Bini Luca L Bargagli Elena E Landi Claudia C

International journal of molecular sciences 20230104 2

Idiopathic pulmonary fibrosis (IPF) is a form of chronic and irreversible fibrosing interstitial pneumonia of unknown etiology. Although antifibrotic treatments have shown a reduction of lung function decline and a slow disease progression, IPF is characterize by a very high mortality. Emerging evidence suggests that IPF increases the risk of lung carcinogenesis. Both diseases show similarities in terms of risk factors, such as history of smoking, concomitant emphysema, and viral infections, bes ...[more]

PMID: 36674438

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Project description:Intratracheal application of bleomycin is known to induce inflammatory and fibrotic reactions in the lung within a short period of time and histological features include infiltration of inflammatory cells, collagen deposition and obliteration of alveolar spaces. Because some of these features are found in patients with idiopathic pulmonary fibrosis (IPF), the bleomycin-induced lung fibrosis animal model is commonly used. However, exploratory treatments that were successfully used in this animal model and progressed to clinical trials lacked significant efficacy in humans. Here, the bleomycin-induced rat lung fibrosis model was studied using whole genome expression data that was collected at various time points and the relevance to human disease was evaluated through comparison with whole genome expression data from IPF patient-derived lung biopsies. The highest gene expression correlation between both species was observed in animals 7 days after bleomycin instillation. These gene expression signatures helped to identify a set of twelve novel disease-relevant translational gene markers that were able to separate IPF patients from controls. Furthermore, three Wnt/-catenin pathway-related genes that belong to this translational gene marker set showed, together with clinical diffusing capacity of the lung for carbon monoxide (DLCO) measurements, the potential to stratify IPF patients according to disease severity. Pirfenidone attenuated a subset of the translational gene markers in the bleomycin-induced fibrosis model, in particular those related to Wnt/-catenin-signaling. This novel translational gene marker panel offers improved possibilities to evaluate disease-modifying efficacy of novel therapeutic concepts in the bleomycin-induced rat lung fibrosis model and could be applied as a diagnostic and prognostic tool for IPF patient care. Comparison of bleomycin-treated and control rats after 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 8 weeks; 5 animals per group

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