Oral Presentation Australia and New Zealand Society for Extracellular Vesicles Conference 2025

Differential expression of extracellular vesicle-associated microRNAs in lung cancer: insights from small RNA sequencing (126902)

Jazmin M Guayco Sigcha 1 , Henry Marshall 1 , Kwun Fong 1 , Ian Yang 1 , Kelly Tian Mun Chee 1
  1. University of Queensland Thoracic Research Centre and The Prince Charles Hospital, Brisbane, QLD, Australia

Background 

Extracellular vesicles (EVs) are lipid bilayer-enclosed particles released by cells that carry proteins, lipids, and nucleic acids, including microRNAs (miRNAs) [1,2]. Encapsulation within EVs protects miRNAs from enzymatic degradation, allowing their detection in blood and other body fluids [3,4]. This stability makes EV-associated miRNAs promising non-invasive biomarkers for disease detection, including lung cancer. In particular, EV-miRNAs could serve as valuable tools for the early detection of lung cancer in high-risk individuals, such as older population and smokers, who are more susceptible to developing lung cancer.

Aim 
To identify differentially expressed EV-associated miRNAs in individuals with lung cancer compared to high-risk healthy individuals. 

Methods 
Serum samples from patients with early stage (I-II) lung cancer (n=6) and high-risk healthy individuals (n=6) underwent EV isolation and RNA extraction. Small RNA libraries were prepared and sequenced (~20 million reads per sample). Reads were trimmed, mapped, and quantified using the miRDeep2 pipeline on Galaxy Australia. Differential expression analysis was performed using the DESeq2 tool with default parameters. 

Results 
Several miRNAs were significantly dysregulated in lung cancer samples (adjusted p < 0.05, |log2FC| > 1). Upregulated miRNAs included hsa-miR-1246, hsa-miR-100-5p, and hsa-miR-205-5p, while hsa-miR-142-3p, hsa-miR-10b-5p, and hsa-miR-150-5p were downregulated. Notably, these miRNAs were not differentially expressed in the EV-depleted serum, indicating that their dysregulation is specific to EV fractions and suggesting their potential as EV-associated biomarkers for lung cancer.  

Conclusions 

Our findings indicate that specific miRNAs are dysregulated in EVs from lung cancer patients but not in EV-depleted serum. This EV-specific expression profile highlights the potential of EV-derived miRNAs as non-invasive biomarkers for lung cancer detection, subject to confirmation in larger cohorts.  

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