By contrast, alterations in PTEN, TP53, and SMAD4 should be considered exploratory, as they showed differential expression but lacked comparable diagnostic, prognostic, or treatment-associated strength.<h4>Conclusions</h4>EBC-based cfRNA profiling provides a feasible, non-invasive approach for molecular characterization of advanced lung adenocarcinoma. Here, SMAD4 is linked to lung adenocarcinoma.