Identification of lung adenocarcinoma-specific exosome RNAs in peripheral blood by RNA-Seq analysis

X.-Q. Liu, A. Tufman, R. Kiefl, G.-F. Li, Q.-L. Ma, R.M. Huber

Department of Internal Medicine V, Division of Respiratory Medicine and Thoracic Oncology, Ludwig-Maximilians University (LMU), Thoracic Oncology Centre Munich; Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research (DZL), Munich, Bavaria, Germany. huber@med.uni-muenchen.de

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• Oncology

OBJECTIVE: Several plasma-derived exosome RNAs have been identified as key regulators in cancer development. They have been considered as potential biomarkers for a non-invasive “liquid biopsy” to diagnose and assess the progression of cancer. This study aimed to identify human lung adenocarcinoma-specific exosome RNAs in peripheral blood, while assessing the feasibility and efficiency of this recently developed deep-sequencing technology for transcriptome profiling.

PATIENTS AND METHODS: Plasma-derived exosome RNAs were isolated from 13 lung adenocarcinoma patients, 3 patients with benign lung diseases, and 15 healthy volunteers. RNA-seq analysis of ribosomal RNA-depleted total RNA was performed. RNAs differentially expressed between lung adenocarcinoma and benign lung diseases or healthy volunteers were identified, followed by GO and KEGG pathway enrichment analyses for the identification of key exosome RNAs associated with lung adenocarcinomas.

RESULTS: Significant differentially expressed RNAs, such as UDP glucuronosyltransferase family 1 member A1 (UGT1A1) and BAI1-associated protein 2 like 1 (BAIAP2L1), were identified as differentially expressed between lung adenocarcinoma patients and patients with benign lung diseases. Eight pseudogenes, including Tropomyosin 1 (Alpha) Pseudogene (LOC100129096), Prothymosin, Alpha Pseudogene 2 (PTMAP2), Cell Division Cycle 14C, Pseudogene (CDC14C), Tropomyosin 1 (Alpha) Pseudogene (LOC643634), Ferritin Heavy Chain 1 Pseudogene 2 (FTH1P2), Actin Related Protein 2/3 Complex Subunit 3 Pseudogene 3 (ARPC3P3), Ferritin Heavy Chain 1 Pseudogene 11 (FTH1P11), and Prothymosin Alpha Pseudogene 5 (PTMAP5) were identified from plasma-derived exosomes in lung adenocarcinoma patients, who were more abundant/detectable than healthy volunteers.

CONCLUSIONS: Our data indicate that plasma-derived exosome RNAs, UGT1A1, and BAIAP2L1, as well as the eight isolated pseudogenes could serve as diagnostic and prognostic biomarkers for an effective non-invasive “liquid biopsy” of lung adenocarcinomas.

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