Lung cancer remains a significant challenge in oncology, with poor prognosis for patients, especially those with advanced-stage disease. The phenomenon of tumor spread through air spaces (STAS) in pulmonary cancer has garnered attention for its association with aggressive tumor behavior and adverse clinical outcomes. Spread through air spaces identification has been highly debatable on scientific community as an important prognostic feature for distant and locoregional recurrence and as a key player in the differential diagnosis and selection of the appropriate treatment. The aim of this study is to unravel the complexities of STAS-positive lung adenocarcinoma (LUAD) diagnosis and treatment options. For that, we intend to (1) isolate primary lung cancer tissues from early-stages lung adenocarcinoma to fabricate organoid in vitro models and (2) evaluate the microRNA (miRNA) profile of tumor and healthy tissue samples. This is a Hybrid (prospective and retrospective) observational clinical study with a nested translational study.