Peripheral Extracellular Vesicles for Diagnosis and Prognosis of Resectable Lung Cancer: The LUCEx Study Protocol

<b>Background/Objectives:</b> Lung cancer is the primary cause of cancer-related deaths. Most patients are typically diagnosed at advanced stages. Low-dose computed tomography (LDCT) has been proven to reduce lung cancer mortality, but screening programs using LDCT are associated with a high number of false positives and unnecessary thoracotomies. It is therefore imperative that a certain diagnosis is refined, especially in cases of solitary pulmonary nodules that are difficult to technically access for an accurate preoperative diagnosis. Extracellular vesicles (EVs) involved in intercellular communication may be an innovative biomarker for diagnosis and therapeutic strategies in lung cancer, regarding their ability to carry tumor-specific cargo. The aim of the LUCEx study is to determine if extracellular vesicle cargoes from both lung tissue and blood could provide complementary information to screen lung cancer patients and enable personalized follow-up after the surgery. <b>Methods:</b> The LUCEx study is a prospective study aiming to recruit 600 patients with lung cancer and 50 control subjects (false positives) undergoing surgery after diagnostic imaging for suspected pulmonary nodules using computed tomography (CT) scans. These patients will undergo curative surgery at the Department of Thoracic Surgery of the Miguel Servet Hospital in Zaragoza, Spain, and will be followed-up for at least 5 years. At baseline, samples from both tumor distal lung tissue and preoperative peripheral blood will be collected and processed to compare the quantity and content of EVs, particularly their micro-RNA (miRNA) cargo. At the third and fifth years of follow-up, CT scans, functional respiratory tests, and blood extractions will be performed. <b>Discussion:</b> Extracellular vesicles and their miRNA have emerged as promising tools for the diagnosis and prognosis of several diseases, including cancer. The LUCEx study, based on an observational clinical cohort, aims to understand the role of these vesicles and their translational potential as complementary tools for imaging diagnosis and prognosis.