Identification of a Competing Endogenous RNA Network Related to Immune Signature in Lung Adenocarcinoma

Front Genet. 2021 Jun 3:12:665555. doi: 10.3389/fgene.2021.665555. eCollection 2021.

Abstract

Background: 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.

Methods: 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.

Results: 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 (R = -0.17), TEK and resting mast cells (R = 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.

Conclusion: We elucidated two immune-related ceRNA networks in LUAD progression, which can be considered as immunotherapy targets for this disease.

Keywords: ceRNA; integrated analysis; lung adenocarcinoma; overall survival; tumor infiltrating immune cells.