RNA sequencing analysis of lung samples of control and irradiated animals

Purpose: Radiation-induced lung injury (RILI) is a progressive condition, with an early phase, radiation pneumonitis (RP), and a late phase, lung fibrosis (LF). RILI may occur after partial body ionizing radiation exposures or by internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aims to provide new insights into the pathogenesis and progression of RILI in the non-human primate (NHP) rhesus macaque model. Methods:We used an integrative approach to understand RILI and its evolution at clinical and molecular levels in seventeen NHPs exposed to10 Gy of whole thorax irradiation in comparison to three sham-irradiated control NHPs. Lung samples were collected at necropsy for molecular and histopathological analyses using RNA sequencing and immunohistochemistry Results: Our data enhances understanding of RILI in non-survivors and survivors in a NHP model. RNA sequencing highlighted the role of SERPINA3, ATP12A, GJB2, CLDN10, TOX3, LPA as possible biomarkers and potential therapeutic targets of RILI. Their differential expression in nonsurvivors and survivors correlated with the severity of the disease. Overall design: Snap frozen lung samples were selected from 3 lung regions (per animal) from 4 irradiated non-survivor animals (total 12 samples), 4 irradiated survivor animals (total 12 samples) and 2 regions (per animal) from 3 control animals (total 6 samples) for RNA extraction and sequencing.