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

## TL;DR

Exosomal LINE-1 mRNA can distinguish lung cancer subtypes and patient characteristics, offering a non-invasive diagnostic tool for better cancer management.

## Contribution

Exosomal LINE-1 mRNA is shown to be a novel, non-invasive biomarker for NSCLC classification and clinical profiling.

## Key findings

- LINE-1 ORF1 and ORF2 mRNA levels correlate with NSCLC subtypes, tumor stage, and patient characteristics.
- Receiver operating characteristic analyses confirmed the diagnostic accuracy of LINE-1 mRNA for NSCLC subtypes.
- LINE-1 mRNA shows strong potential as a liquid biopsy biomarker for precision cancer management.

## Abstract

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.

Exosomal long interspersed nuclear element‐1 (LINE‐1) analytes exhibit distinct expression profiles across histologic subtypes of non‐small cell lung cancer (NSCLC) and demonstrate significant associations with clinicopathological characteristics. These findings underscore the potential of exosomal LINE‐1 mRNA as a minimally invasive biomarker for NSCLC stratification, prognostic evaluation, and personalized therapeutic management.