RNA-seq analysis of nintedanib effects on interstitial pneumonia in preoperative NSCLC patients

Abstract

Background

Lung cancer patients with interstitial pneumonia (IP) have limited treatment options due to the risks associated with therapeutic intervention. The underlying causes of IP in these patients are diverse, and there is currently no detailed molecular pathological classification or an established understanding of the effectiveness of anti-fibrotic medications such as nintedanib. This study aimed to elucidate the mechanism of action of nintedanib by analyzing differential RNA expression between normal and fibrotic lung tissues from lung cancer patients with IP.

Methods

RNA was analyzed from the non-tumor lung tissue of 7 patients with IP who received nintedanib before surgery. Non-tumor lung tissue was obtained from 12 lung cancer patients without IP complications who underwent radical surgery between 2017 and 2022 from the tissue bank of our institution. Fibrotic lung tissue from six IP patients who received nintedanib before surgery and 7 who did not (where RNA analysis was possible). Gene expression and microenvironmental analyses were performed using RNA sequencing data.

Results

Nintedanib modulated inflammation in non-tumor lung tissue, suppressing PLA2G2D and upregulating CST2 and MMP11, suggesting minimal impact on normal tissue and a favorable safety profile. In fibrotic lung lesions, nintedanib suppressed MUC6, ITLN1, and AREG expression. xCell2 analysis indicated reduced plasma cells and increased smooth muscle, muscle, adipocyte, and endothelial cells, suggesting normalization of tissue remodeling.

Interpritation

Nintedanib appears to exert anti-inflammatory effects and promote tissue repair in non-tumor lung, while facilitating tissue remodeling in fibrotic areas, indicating potential benefits in patients with interstitial pneumonia and lung cancer.