Zhu Ting, Yu Yong, Liu Jun, Ren Kaiming
Shengjing Hospital of China Medical University, Shenyang, China.
Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
Front Genet. 2021 Jun 3;12:665555. doi: 10.3389/fgene.2021.665555. eCollection 2021.
The establishment of immunotherapy has led to a new era in oncotherapy. But the signature of immune-related genes (IRGs) in LUAD remains to be elucidated. Here we use integrated analysis to identify IRGs roles in immune signature and detect their relationship with competing endogenous RNA (ceRNA) networks in LUAD progression.
By analyzing the RNA-seq data from different platforms, we recognized the differentially expressed genes (DEGs) of each platform and screened out the top 20 hub IRGs related to immune responses. Then, we applied the CIBERSORT algorithm to explore the landscape of tumor-infiltrating immune cells (TILs) in LUAD and their connection with hub genes. Next, we predicted and validated the upstream miRNAs and lncRNAs according to their expression and prognostic roles. Finally, we constructed and validated an immune-related ceRNA network by co-expression analysis.
A total of 71 IRGs were identified among 248 DEGs, which play key roles in immune responses. CIBERSORT analysis showed that six hub genes were closely related to TILs, such as SPP1 and naive B cells ( = -0.17), TEK and resting mast cells ( = 0.37). Stepwise prediction and validation from mRNA to lncRNA, including 6 hub genes, 5 miRNAs, and 9 lncRNAs, were applied to construct a ceRNA network. Ultimately, we confirmed the TMPO-AS1/miR-126-5p/SPP1 and CARD8-AS1/miR-21-5p/TEK as immune-related ceRNA networks in LUAD progression.
We elucidated two immune-related ceRNA networks in LUAD progression, which can be considered as immunotherapy targets for this disease.
免疫疗法的建立开创了肿瘤治疗的新纪元。但肺腺癌中免疫相关基因（IRGs）的特征仍有待阐明。在此，我们运用综合分析来确定IRGs在免疫特征中的作用，并检测它们在肺腺癌进展过程中与竞争性内源RNA（ceRNA）网络的关系。
通过分析来自不同平台的RNA测序数据，我们识别出每个平台的差异表达基因（DEGs），并筛选出与免疫反应相关的前20个核心IRGs。然后，我们应用CIBERSORT算法来探究肺腺癌中肿瘤浸润免疫细胞（TILs）的格局及其与核心基因的联系。接下来，我们根据上游miRNA和lncRNA的表达及预后作用进行预测和验证。最后，我们通过共表达分析构建并验证了一个免疫相关的ceRNA网络。
在248个DEGs中总共鉴定出71个IRGs，它们在免疫反应中起关键作用。CIBERSORT分析表明，6个核心基因与TILs密切相关，如SPP1与幼稚B细胞（r = -0.17）、TEK与静息肥大细胞（r = 0.37）。从mRNA到lncRNA进行逐步预测和验证，包括6个核心基因、5个miRNA和9个lncRNA，用于构建ceRNA网络。最终，我们确认TMPO-AS1/miR-126-5p/SPP1和CARD8-AS1/miR-21-5p/TEK是肺腺癌进展过程中免疫相关的ceRNA网络。
我们阐明了肺腺癌进展过程中的两个免疫相关ceRNA网络，它们可被视为该疾病的免疫治疗靶点。
