Abstract
BackgroundDelayed diagnosis is the main obstacle to improve prognosis of non-small cell lung cancer (NSCLC). Novel biomarkers for the diagnosis of NSCLC are urgently needed. This study aimed to identify the specific exosomal miRNAs with diagnostic and prognostic potential in NSCLC patients.Materials and MethodsTransmission electron microscopy (TEM), qNano and western blots were used to characterize the exosomes isolated from the serum of NSCLC patients (n=330) and healthy donors (n=312) by ultracentrifugation. Exosomal miRNAs were profiled by miRNA microarrays and verified by quantitative PCR (qPCR). The diagnostic accuracy was determined by receiver operating characteristic (ROC) analysis.ResultsA total of differential 22 miRNAs were screened out based on P < 0.05 and fold difference>2.0 by miRNA microarrays, among which, exosomal miR-5684 and miR-125b-5p were significantly down-regulated in NSCLC patients compared to healthy donors, processing favorable diagnostic efficiency for (early) NSCLC. Importantly, the exosomal miR-125b-5p were associated with metastasis (P < 0.0001), chemotherapeutic effect (P=0.007) and survival (P=0.008).ConclusionExosomal miR-5684 and miR-125b-5p levels are significantly down-regulated in NSCLC patients, and serve as the promising diagnostic and prognostic biomarkers for NSCLC.
Highlights
Non-small cell lung cancer (NSCLC), the most common type of lung cancer which accounts for about 80% of all lung cancer, is the leading cause of cancer-related deaths worldwide [1]
The serum exosomes isolated from NSCLC patients and healthy donors were characterized by Transmission Electron Microscopy (TEM), qNano and western blots
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses further predicted 30 signaling pathways that were enriched among these differentially expressed miRNAs (DEMs) (Figures 2B, C), among which retinoic acid receptor binding and long-term potentiation were likely involved in the tumorigenesis and development of NSCLC
Summary
Non-small cell lung cancer (NSCLC), the most common type of lung cancer which accounts for about 80% of all lung cancer, is the leading cause of cancer-related deaths worldwide [1]. There is an urgent need for more reliable biomarkers for the early diagnosis of NSCLC and the monitoring of its progression and response to anti-cancer therapy. Dysregulation of miRNAs expression plays critical roles in the development and progression of different cancers by affecting multiple cellular processes including cell proliferation, apoptosis, survival, invasion, metastasis, and chemotherapeutic resistance [5, 6]. The differentially expressed circulating miRNAs between lung cancer patients and healthy humans can be used as novel biomarkers for diagnosis, serving the non-invasive biomarkers for NSCLC. Delayed diagnosis is the main obstacle to improve prognosis of non-small cell lung cancer (NSCLC). Novel biomarkers for the diagnosis of NSCLC are urgently needed. This study aimed to identify the specific exosomal miRNAs with diagnostic and prognostic potential in NSCLC patients
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