Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer

Abstract

Lung cancer is a malignant disease with high mortality and poor prognosis, frequently diagnosed at advanced stages. Nowadays, immense progress in treatment has been achieved. However, the present scenario continues to be critical, and a full comprehension of tumor progression mechanisms is required, with exosomes being potentially relevant players. Exosomes are membranous vesicles that contain biological information, which can be transported cell-to-cell and modulate relevant processes in the hallmarks of cancer. The present research aims to characterize the exosomes’ cargo and study their role in NSCLC to identify biomarkers. We analyzed exosomes secreted by primary cultures and cell lines, grown in monolayer and tumorsphere formations. Exosomal DNA content showed molecular alterations, whereas RNA high-throughput analysis resulted in a pattern of differentially expressed genes depending on histology. The most significant differences were found in XAGE1B, CABYR, NKX2-1, SEPP1, CAPRIN1, and RIOK3 genes when samples from two independent cohorts of resected NSCLC patients were analyzed. We identified and validated biomarkers for adenocarcinoma and squamous cell carcinoma. Our results could represent a relevant contribution concerning exosomes in clinical practice, allowing for the identification of biomarkers that provide information regarding tumor features, prognosis and clinical behavior of the disease.

Soluble galectin‐3 as a microenvironment‐relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma

“…EVs are an important part of TME acting as effective signaling molecules between cancer cells and the surrounding cells [ 47 ]. We had previously performed an exhaustive characterization of NSCLC EVs revealing that EVs cargo can reflect the molecular signatures and their capacity to be used as a tool for diagnosis and prognosis [ 48 ]. In view of potential role of secreted Gal‐3 as an immunomodulator molecule, we analyzed EVs‐associated Gal‐3 in our cohort of cell cultures.…”

“…Despite this, some limitations such as partial clinical outcome information which might lead to some uncertainties in the results. Nevertheless, TCGA database is public, provide massive information and allows carry out in silico analysis such performed previously in our laboratory [ 22 , 48 ].…”

Circulating plasma miR-23b-3p as a biomarker target for idiopathic Parkinson's disease: comparison with small extracellular vesicle miRNA

“…Although, the cargo contained within these sEVs are a variety including proteins, lipids and nucleic acids (Zhang et al, 2019b ). The miRNAs, a class of small non-coding RNAs, have emerged as the most studied cargo owing to their diverse function and multiple targets (Duréndez-Sáez et al, 2022 ). The miRNAs are released by cells in extracellular space encapsulated within the small EVs or without encapsulation in a vesicle-free form (Lee et al, 2019 ).…”

Characterization of Tumor Cells and Immune Microenvironment Interactions in Non Small Cell Lung Cancer. Translational implications

“…Regarding ctDNA, few studies have been conducted to date, but it appears that high levels of ctDNA may be indicative of a worse prognosis (Abbosh et al, 2017). The potential of EVs to be a source of biomarkers for prognosis has also been proposed (Duréndez-Sáez et al, 2022).…”

“…These EVs play a vital role in the TME by contributing as potent signaling molecules in the communication between cancer cells and neighboring cells (Dang et al, 2016). In our previous laboratory work, we conducted a comprehensive characterization on NSCLC EVs, revealing that the cargo within EVs can reflect molecular signatures and serve as a valuable tool for both diagnosis and prognosis (Duréndez-Sáez et al, 2022).…”