Extracellular RNA profiles in non-small cell lung cancer plasma

Yaojun Ni; Wenhao Zhang; Guang Mu; Yan Gu; Hongchang Wang; Ke Wei; Yang Xia; Xueying Xie; Qinyu Ge; Tan Tan; Jun Wang

doi:10.21037/jtd-23-517

Extracellular RNA profiles in non-small cell lung cancer plasma

J Thorac Dis. 2023 May 30;15(5):2742-2753. doi: 10.21037/jtd-23-517. Epub 2023 May 25.

Authors

Yaojun Ni^#^{1

2}, Wenhao Zhang^#¹, Guang Mu^#¹, Yan Gu¹, Hongchang Wang¹, Ke Wei¹, Yang Xia¹, Xueying Xie³, Qinyu Ge³, Tan Tan⁴, Jun Wang¹

Affiliations

¹ Department of Thoracic Surgery, Jiangsu Province People's Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Thoracic Surgery, Huai'an First Hospital Affiliated to Nanjing Medical University, Huai'an, China.
³ State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
⁴ Department of Thoracic Surgery, Geriatric Hospital of Nanjing Medical University, Nanjing, China.

^# Contributed equally.

Abstract

Background: Non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. The early detection of high-risk patients is essential to improve patient prognosis. Thus, the identification of a non-invasive, non-radiative, convenient, and fast diagnostic approach should be a top priority in NSCLC research. Circulating extracellular RNAs (exRNAs) in the plasma are potential biomarkers for NSCLC.

Methods: We used RNA-sequencing (RNA-seq) technology to explore the NSCLC-related RNAs, especially the circular RNAs (circRNAs). The circRNA-targeted micro RNAs (miRNAs) were predicted using 3 circRNA databases [i.e., the Cancer-Specific CircRNA Database (CSCD), circBank, and Circular RNA Interactome]. The circRNA-miRNA-messenger RNA (mRNA) network was constructed using Cytoscape V3.8.0 (Cytoscape Consortium, San Diego, CA, USA). The expression levels of some differentially expressed genes were validated by a quantitative real-time polymerase chain reaction (qRT-PCR) analysis.

Results: The results showed that the RNA biotypes of the mitochondrial ribosomal RNAs (mt-rRNAs) and mitochondrial transfer RNAs (mt-tRNAs) were upregulated in the NSCLC plasma. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms of the differentially expressed transcripts of NSCLC included oxidative phosphorylation, proton transmembrane transport, and the response to oxidative stress. Additionally, the qRT-PCR validation indicated that hsa_circ_0000722 had significantly higher expression in the NSCLC plasma than the control plasma, but hsa_circ_0006156 did not differ between the NSCLC plasma and the control plasma. The expression levels of miR-324-5p and miR-326 were higher in the NSCLC plasma than the control plasma.

Conclusions: In this study, an exRNA-sequencing strategy was used to identify the expression of NSCLC-specific transcription factors in clinical plasma samples, and hsa_circ_0000722 and hsa-miR-324-5p were identified as potential biomarkers in NSCLC.

Keywords: Non-small cell lung cancer (NSCLC); expression; hsa-miR-324-5p; hsa_circ_0000722.