Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Sci Rep. 2021 May 26;11(1):11056. doi: 10.1038/s41598-021-90755-w.
To identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan-Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, and has-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that the FKBP3 was associated with Monocytes and Macrophages M1, and the GPI was obviously related with Monocytes and Macrophages M1. Besides, the LOXL2 was associated with Monocytes and Activated mast cells, and the IL22RA1 was significantly associated with Monocytes and Macrophages M1, while the GPR37 and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.
为了确定竞争性内源性 RNA (ceRNA) 的预后生物标志物,并探讨可能成为肺腺癌潜在预后因素的肿瘤浸润免疫细胞 (TIICs)。此外,我们还试图解释 ceRNA 和 TIICs 之间的串扰,以探讨肺腺癌涉及的分子机制。肺腺癌的转录组数据来自癌症基因组图谱 (TCGA) 数据库,并基于 starBase 分析了差异表达的 miRNA-lncRNA 和 miRNA-mRNA 的超几何相关性。此外,使用 Kaplan-Meier 生存和 Cox 回归模型分析来识别预后 ceRNA 网络和 TIICs。进行相关性分析以分析 ceRNA 网络和 TIICs 之间的相关性。在肿瘤组织和正常组织之间差异表达的 RNA 中,共检测到 190 个 miRNA、224 个 lncRNA 和 3024 个 mRNA,构建的 ceRNA 网络包含 5 个 lncRNA、92 个 mRNA 和 10 个 miRNA。然后,将六个预后 RNA (FKBP3、GPI、LOXL2、IL22RA1、GPR37 和 has-miR-148a-3p) 视为 ceRNA 网络中构建预后预测模型的关键成员,并鉴定出三种 TIICs(单核细胞、M1 型巨噬细胞、活化肥大细胞)与肺腺癌的预后显著相关。相关性分析表明,FKBP3 与单核细胞和 M1 型巨噬细胞相关,GPI 与单核细胞和 M1 型巨噬细胞明显相关。此外,LOXL2 与单核细胞和活化的肥大细胞相关,IL22RA1 与单核细胞和 M1 型巨噬细胞显著相关,而 GPR37 与 M1 型巨噬细胞密切相关。构建的 ceRNA 网络和鉴定的单核细胞、M1 型巨噬细胞和活化的肥大细胞均为肺腺癌的预后因素。此外,ceRNA 网络和 TIICs 之间的串扰可能是涉及的潜在分子机制。