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

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.

Development of an m6A‐Related lncRNAs Signature Predicts Tumor Stemness and Prognosis for Low‐Grade Glioma Patients

“…As the risk score alone may not be sufficient for predicting LGG prognosis, we followed the methods of Guo et al [ 19 ] to construct a nomogram in combination with other clinical features. In accordance with the multivariable Cox regression model ( Figure 4(a) ), age, grade, and risk score were independent indicators of LGG OS.…”

“…The nomogram analysis was performed following the methods of Guo et al [ 19 ]. Clinical features, including age, sex, grade, IDH mutation, 1p/19q codeletion, MGMT methylation, and our risk score, were included in the multivariable Cox regression model in the TCGA-LGG training dataset.…”

Systematic analysis of expression profiles of HMGB family members for prognostic application in non-small cell lung cancer

“…Immune infiltration in the tumor microenvironment is closely related to clinical outcomes in cancers, including NSCLC ( Fridman et al, 2011 ; Chen et al, 2019 ; Guo et al, 2022 ). We used the ssGSEA algorithm on the XIANTAO platform ( www.xiantao.love ) to assess the correlation between expression of HMGB genes and immune infiltration profiles of 24 types of infiltrating immune cells in NSCLC samples.…”