Radioproteomics stratifies molecular response to antifibrotic treatment in pulmonary fibrosis

<p><span><span><span>The dataset contains underlying data and code for reproduction of the main findings of this study.</span></span></span></p> <h2><span><span>Abstract</span></span></h2> <p><span><span>Antifibrotic therapy with&nbsp;</span><span>nintedanib</span><span> is the clinical </span><span>mainstay</span><span> in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, </span><span>provides</span><span> quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we used an integrative analysis of radiomic and proteomic profiles (</span><span>radioproteomics</span><span>) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to </span><span>nintedanib</span><span> in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed two distinct imaging phenotypes in mice treated with </span><span>nintedanib</span><span>, contrary to conventional densitometry readouts</span><span>, which showed a more</span><span> uniform response. Integrative analysis of delta radiomics and proteomics </span><span>demonstrated</span><span> that these phenotypes reflected different treatment response states, as further </span><span>evidenced</span><span> on transcriptional and cellular levels</span><span>. Importantly, </span><span>radioproteomic</span><span>s</span><span> signatures paralleled disease- and drug related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of </span><span>nintedanib</span><span>-treated fibrosing ILD patients, accurately stratified patients based on their extent of lung function decline. </span><span>In conclusion, delta radiomics has great potential to serve as a non-invasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD.</span><span> This could pave the way for personalized treatment strategies and improved patient outcomes.</span></span><span><span><span> </span></span></span></p> <p><span>&nbsp;</span></p> <p>&nbsp;</p>