The aim of this study was to identify miRNAs in plasma exosomes as noninvasive biomarkers for the early diagnosis of lung adenocarcinoma (LUAD). First, exosomal miRNA profiling of three patients with early LUAD and three patients with benign lung disease were screened by next‐generation sequencing (NGS) method. Sequencing results showed that 154 exosomal miRNAs were differentially expressed in the plasma of LUAD patients, among which 68 miRNAs were up‐regulated and 86 miRNAs were down‐regulated. GSE137140 is a GEO database containing serum miRNAs sequencing data from 1566 lung cancer patients and 1774 non‐cancer patients controls. When comparing the sequencing data, it was found that most miRNAs (37/68) up‐regulated in our LUAD group were also significantly up‐regulated in GSE137140, suggesting that circulating miRNAs in lung cancer patients may be enriched in plasma exosomes. In GSE137140, the AUC of the combination of hsa‐miR‐103b, hsa‐miR‐29c‐5p and hsa‐miR‐877‐5p was 0.873, showing great potential as new tumor markers. To our knowledge, these three exosomal miRNAs have not been reported in lung cancer research. Furthermore, bioinformatics tools were used to analyze the target genes of three candidate miRNAs, which were indeed closely related to the occurrence and development of lung cancer. Bioinformatics algorithms deduced a highly conserved sequence in the 3’‐UTR of SFRP4, FOXM1 and TMEM98 that could be bound with miR‐103b/877‐5p/29c‐5p. A luciferase assay indicated that miR‐103b/877‐5p/29c‐5p directly targeted the 3’‐UTR of SFRP4, FOXM1 and TMEM98, respectively. Finally, three candidate miRNAs were validated by qRT‐PCR in 17 early LUAD samples and 17 control plasma samples. Integration of bioinformatics analysis and experimental validation identifies, this study provides novel insights into miRNA‐related networks in LUAD. Hsa‐miR‐103b, hsa‐miR‐29c‐5p, and hsa‐miR‐877‐5p may be used as diagnostic biomarkers for early LUAD.

N6-methyladenosine (m6A) RNA modification is the most abundant modification method in mRNA, and it plays an important role in the occurrence and development of many cancers. This paper mainly discusses the role of m6A RNA methylation regulators in lung adenocarcinoma (LUAD) to identify novel prognostic biomarkers. The gene expression data of 19 m6A methylation regulators in LUAD patients and its relevant clinical parameters were extracted from The Cancer Genome Atlas (TCGA) database. We selected three significantly differentially expressed m6A regulators in LUAD to construct the risk signature, and evaluated its prognostic prediction efficiency using the receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the independent prognostic significance of the risk signature. The ROC curve indicated that the area under the curve (AUC) was 0.659, which means that the risk signature had a good prediction efficiency. The results of the Kaplan–Meier survival analysis and Cox regression analysis showed that the risk score can be used as an independent prognostic factor for LUAD. In addition, we explored the differential signaling pathways and cellular processes related to m6A methylation regulators in LUAD.

Introduction: Lung cancer has long been at the forefront of all cancers in terms of incidence and mortality. Lung adenocarcinoma is the most common type of lung cancer, accounting for 40% of all lung cancer types. Exosomes can act as biomarkers of tumors and thus play an important role.Methods: In this article, high-throughput sequencing of miRNAs in plasma exosomes from lung adenocarcinoma patients and healthy individuals was performed to obtain 87 upregulated miRNAs, which were then combined with data from the GSE137140 database uploaded by others for screening. The database included 1566 preoperative lung cancer patients, 180 postoperative patients, and 1774 non-cancerous controls. We overlapped the miRNAs upregulated in the serum of lung cancer patients in the database relative to those of non-cancer controls and post-operative patients with the upregulated miRNAs obtained from our next-generation sequencing to obtain nine miRNAs. Two miRNAs that were not reported as tumor markers in lung cancer, hsa-miR-4454 and hsa-miR-619-5p, were selected from them and then validated by qRT-PCR, and further analysis of miRNAs was performed using bioinformatics.Results: Real-time quantitative PCR showed that the expression levels of hsa-miR-4454 and hsa-miR-619-5p in plasma exosomes of patients with lung adenocarcinoma were significantly up-regulated. The AUC values of hsa-miR-619-5p and hsa-miR-4454 were 0.906 and 0.975, respectively, both greater than 0.5, showing good performance. The target genes of miRNAs were screened by bioinformatics methods, and the regulatory network between miRNAs and lncRNAs and mRNAs was studied.Discussion: Our work demonstrated that hsa-miR-4454 and hsa-miR-619-5p have the potential to be used as biomarkers for the early diagnosis of lung adenocarcinoma.