Abstract
BackgroundThis study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC).MethodsThe circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA–miRNA–mRNA). Finally, the functional analysis and drug–gene interaction analysis of mRNAs in the ceRNA network was performed.ResultsA total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA–miRNA and 674 miRNA–mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA–miRNA–mRNA network was constructed, containing 5 miRNA–circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA–mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs.ConclusionThree circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.
Highlights
This study aimed to identify potential circular ribonucleic acid signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC)
Construction of DEcircRNA–miRNA–mRNA network and functional analysis In the final step, we obtained the mRNAs that were significantly associated with prognosis
Identification of DEcircRNAs A total of 35 DEcircRNAs (30 up-regulated DEcircRNAs and 5 down-regulated DEcircRNAs) were identified from the LAC tumour tissues and the adjacent normal tissues as per the screening criteria described in the Methods section
Summary
This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). Zhu et al analysed a circRNA microarray dataset and found that 59 circRNAs had differential expression in LAC samples than in nontumour samples. They noted that in most cases, up-regulated hsa_circ_0013958 was strongly related to the TNM stage and lymphatic metastasis, indicating that this circRNA might be a potential target for the early detection of LAC [9]. A previous study performed a circRNA microarray analysis of early-stage LAC using GSE101684 set and identified 357 differentially expressed circRNAs (DEcircRNAs). A comprehensive bioinformatics analysis based on this dataset has not been conducted
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