Proteomics Analysis of Formalin-Fixed Paraffine-Embedded Tissue Reveals Key Proteins Related to Lung Dysfunction in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) severely affects the lung leading to aberrant deposition of extracellular matrix and parenchymal
stiffness with progressive functional derangement. The limited availability of fresh tissues represents one of the major limitations
to study the molecular profiling of IPF lung tissue. The primary aim of this study was to explore the proteomic profiling yield of
archived formalin-fixed paraffin-embedded (FFPE) specimens of IPF lung tissues. We further determined the protein expression
according to respiratory functional decline at the time of biopsy. The total proteins isolated from 11 FFPE samples of IPF patients
compared to 3 FFPE samples from a non-fibrotic lung defined as controls, were subjected to label-free quantitative proteomic
analysis by liquid chromatography-mass spectrometry (LC-MS/MS) and resulted in the detection of about 400 proteins. After the
pairwise comparison between controls and IPF, functional enrichment analysis identified differentially expressed proteins that
were involved in extracellular matrix signaling pathways, focal adhesion and transforming growth factor β (TGF‐β) signaling
pathways strongly associated with IPF onset and progression. Five proteins were significantly over-expressed in the lung of IPF
patients with either advanced disease stage (Stage II) or impaired pulmonary function (FVC<75, DLco<55) compared to controls;
these were lymphocyte cytosolic protein 1 (LCP1), peroxiredoxin-2 (PRDX2), transgelin 2 (TAGLN2), lumican (LUM) and mimecan
(OGN) that might play a key role in the fibrogenic processes. Our work showed that the analysis of FFPE samples was able to
identify key proteins that might be crucial for the IPF pathogenesis. These proteins are correlated with lung carcinogenesis or
involved in the immune landscape of lung cancer, thus making possible common mechanisms between lung carcinogenesis and
fibrosis progression, two pathological conditions at risk for each other in the real life.