Abstract：
OBJECTIVE: To explore an exosome-relevant molecular classification in lung adenocarcinoma (LUAD).
BACKGROUND: Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined.
OBJECTIVE: Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation.
METHODS: MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis.
RESULTS: Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects.
CONCLUSIONS: Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.
BACKGROUND: Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined.
OBJECTIVE: Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation.
METHODS: MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis.
RESULTS: Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects.
CONCLUSIONS: Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.
摘要：
目的：探讨肺腺癌（LUAD）的外泌体相关分子分类。
背景：外泌体基因或相关非编码RNA是癌症治疗和预后的调节因子，但它们在LUAD中的功能尚未确定。
目的：应用外泌体相关RNA网络进行LUAD预后评估的分子分类。
方法:MicroRNA测序数据(miRNA-seq)和RNA测序数据(RNA-seq)来源于癌症基因组图谱(TCGA)。ConsensusCluster-Plus软件包用于基于121个外泌体相关基因的LUAD的分子分型。然后，进行了LIMA包装以探索差异表达的mRNA（DEmRNA），分子分型中差异表达的miRNA（DEmiRNAs）和差异表达的lncRNAs（DElncRNAs），用于构建外泌体驱动的竞争性内源性RNA网络（ceRNA）。显性miRNA,以及靶mRNA，通过COX建模和Kaplan-Meier生存分析进行鉴定。
结果：在LUAD中分类的两个外泌体相关分子簇。C2簇有利于高临床病理，并显示出预后不良的趋势。鉴定了29个lncRNA-miRNA和12个miRNA-mRNA相互作用对。hsa-miR-429是影响LUAD预后的关键miRNA。根据LUAD的相互作用关系和预后作用,鉴定了SNHG6-hsa-miR-429-CHRDL1/CCNA2。SNHG6-hsa-miR-429-CHRDL1发挥致癌作用，和SNHG6-hsa-miR-429-CCNA2发挥促致癌作用。
结论：总体而言，我们的研究确定了LUAD中Exosome驱动的ceRNA网络，SNHG6-hsa-miR-429-CHRDL1/CCNA2轴可能是LUAD的新治疗靶点，我们的研究为LUAD的分子机制提供了新的见解。
背景：外泌体基因或相关非编码RNA是癌症治疗和预后的调节因子，但它们在LUAD中的功能尚未确定。
目的：应用外泌体相关RNA网络进行LUAD预后评估的分子分类。
方法:MicroRNA测序数据(miRNA-seq)和RNA测序数据(RNA-seq)来源于癌症基因组图谱(TCGA)。ConsensusCluster-Plus软件包用于基于121个外泌体相关基因的LUAD的分子分型。然后，进行了LIMA包装以探索差异表达的mRNA（DEmRNA），分子分型中差异表达的miRNA（DEmiRNAs）和差异表达的lncRNAs（DElncRNAs），用于构建外泌体驱动的竞争性内源性RNA网络（ceRNA）。显性miRNA,以及靶mRNA，通过COX建模和Kaplan-Meier生存分析进行鉴定。
结果：在LUAD中分类的两个外泌体相关分子簇。C2簇有利于高临床病理，并显示出预后不良的趋势。鉴定了29个lncRNA-miRNA和12个miRNA-mRNA相互作用对。hsa-miR-429是影响LUAD预后的关键miRNA。根据LUAD的相互作用关系和预后作用,鉴定了SNHG6-hsa-miR-429-CHRDL1/CCNA2。SNHG6-hsa-miR-429-CHRDL1发挥致癌作用，和SNHG6-hsa-miR-429-CCNA2发挥促致癌作用。
结论：总体而言，我们的研究确定了LUAD中Exosome驱动的ceRNA网络，SNHG6-hsa-miR-429-CHRDL1/CCNA2轴可能是LUAD的新治疗靶点，我们的研究为LUAD的分子机制提供了新的见解。
