Prognostic Implications and Immune Infiltration Characteristics of Chromosomal Instability-Related Dysregulated CeRNA in Lung Adenocarcinoma

Shengnan Guo; Tianhao Li; Dahua Xu; Jiankai Xu; Hong Wang; Jian Li; Xiaoman Bi; Meng Cao; Zhizhou Xu; Qianfeng Xia; Ying Cui; Kongning Li

doi:10.3389/fmolb.2022.843640

Prognostic Implications and Immune Infiltration Characteristics of Chromosomal Instability-Related Dysregulated CeRNA in Lung Adenocarcinoma

Front Mol Biosci. 2022 Mar 28:9:843640. doi: 10.3389/fmolb.2022.843640. eCollection 2022.

Authors

Shengnan Guo¹, Tianhao Li¹, Dahua Xu¹, Jiankai Xu², Hong Wang¹, Jian Li², Xiaoman Bi¹, Meng Cao¹, Zhizhou Xu¹, Qianfeng Xia³, Ying Cui², Kongning Li¹

Affiliations

¹ Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Institute of Nephrology Second Affiliated Hospital and Hainan General Hospital, Hainan Medical University, Haikou, China.
² College of Bioinformatics Science and Technology, Cancer Hospital, Harbin Medical University, Harbin, China.
³ Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Control of Tropical Diseases, School of Tropical Medicine, The Second Affiliated Hospital, Hainan Medical University, Haikou, China.

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.

Keywords: chromosomal instability; dysregulated ceRNA; immune microenvironment; lung adenocarcinoma; prognosis.