Exosomal Long Interspersed Nuclear Element‐1 Analytes Discriminate Histologic Subtypes, Sex, and Clinicopathological Characteristics of Patients with Non‐Small Cell Lung Cancer

Lung cancer is the leading cause of cancer‐related mortality worldwide, with lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) representing the most common non‐small cell lung cancer (NSCLC) subtypes. The invasive procedures typically required to obtain specimens for clinical evaluation pose significant risks and can delay patient care. To address these limitations, analysis of cancer‐related biomarkers in circulating exosomes has emerged as a promising liquid biopsy approach. In this study, levels of long interspersed nuclear element‐1 (LINE‐1) mRNA were measured in ostensibly healthy controls and compared with those in patients with LUSC and LUAD. Both LINE‐1 ORF1 and ORF2 mRNA were readily detectable across all cancer stages in both female and male patients, with expression patterns correlating with histologic subtype, tumor stage, tumor size, lymph node involvement, distant metastasis, and smoking status. Receiver operating characteristic analyses confirmed the robustness of this approach in distinguishing NSCLC subtypes and associated clinicopathological features. Collectively, these findings highlight exosomal LINE‐1 mRNA as a readily accessible biomarker for precision profiling of NSCLC. The strong diagnostic and prognostic performance of this liquid biopsy platform underscores its potential to advance the clinical management of patients with NSCLC.