Screening and validation of biomarkers for radiation pneumonitis based on targeted plasma proteomics

ABSTRACT: The absence of reliable biomarkers for predicting the risk and severity of radiation pneumonitis (RP) prior to radiotherapy represents a major clinical challenge, as current tools rely on delayed imaging and lack specificity. The molecular mechanisms that determine why only a subset of patients progress to severe lung injury remain largely unknown. To address this, we conducted a preliminary prospective plasma proteomic profiling in patients with non-small cell lung cancer (NSCLC) before thoracic radiotherapy. Using high-resolution data-independent acquisition (DIA) mass spectrometry, we screened for circulating proteins associated with subsequent RP development. Through this approach and cross-species validation in a murine model of radiation-induced lung injury, we preliminarily identified THEMIS2 as a potential central predictive hub protein. Its baseline plasma level showed a strong correlation with subsequent clinical severity. Critically, while Themis2 was upregulated in irradiated lung tissue, its expression was significantly lower in non-surviving animals compared to survivors. This dual expression pattern supports a preliminary "compensation-exhaustion" hypothesis: elevated baseline THEMIS2 may indicate a pre-sensitized, compensatory immune state potentially associated with higher risk, whereas the failure to sustain this response post-irradiation appears correlated with fatal outcome. Collectively, our preliminary findings suggest THEMIS2 as a novel candidate biomarker that may link pre-treatment risk assessment to post-injury prognosis, implying a potential key mechanism in RP pathogenesis and providing a preliminary molecular basis for early intervention strategies. These findings require validation in larger cohorts.

ORGANISM(S): Homo Sapiens

SUBMITTER: Ping Lei  

PROVIDER: PXD072727 | iProX | Wed Jan 07 00:00:00 GMT 2026

REPOSITORIES: iProX