AUTHOR=Guo Shengnan , Li Tianhao , Xu Dahua , Xu Jiankai , Wang Hong , Li Jian , Bi Xiaoman , Cao Meng , Xu Zhizhou , Xia Qianfeng , Cui Ying , Li Kongning TITLE=Prognostic Implications and Immune Infiltration Characteristics of Chromosomal Instability-Related Dysregulated CeRNA in Lung Adenocarcinoma JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.843640 DOI=10.3389/fmolb.2022.843640 ISSN=2296-889X ABSTRACT=

An accumulating body of research indicates that long-noncoding RNAs (lncRNAs) regulate the target genes and act as competitive endogenous RNAs (ceRNAs) playing an indispensable role in lung adenocarcinoma (LUAD). LUAD is frequently accompanied by the feature of chromosomal instability (CIN); however, CIN-related ceRNAs have not been investigated yet. We systematically analyzed and integrated CIN-related dysregulated ceRNAs characteristics in LUAD samples for the first time. In TCGA LUAD cohort, CIN in tumor samples was significantly higher than that in those of adjacent, and patients with high CIN risk tended to have worse clinical outcomes. We constructed a double-weighted CIN-related dysregulated ceRNA network, in which edge weight and node weight represented the disorder extent of ceRNA and the correlation of RNA expression level and prognosis, respectively. After module mining and analysis, a potential prognostic biomarker composed of 12 RNAs (8 mRNAs and 4 lncRNAs) named CIN-related dysregulated ceRNAs (CRDC) was obtained. The CRDC risk score had a positive relation with clinical stage and CIN, and patients with high CRDC risk scores exhibited poor prognosis. Moreover, CRDC tended to be an independent risk factor with high robustness to overcome the effect of multicollinearity among other explanatory variables for disease-specific survival (DSS) in TCGA and two GEO cohorts. The result of functional analysis indicated that CRDC was involved in multiple cancer progresses, especially immune-related pathways. The patients with lower CRDC risk had higher B cell, T cell CD4+, T cell CD8+, neutrophil, macrophage, and myeloid dendritic cell infiltration than the patients with higher CRDC risk. Meanwhile, patients with lower CRDC risk could get more benefits from immunological therapy. The results suggested that the CRDC could be a potential prognostic biomarker and an immunotherapy predictor for lung adenocarcinoma.