Prognostic Nomogram Based on Circular RNA‐Associated Competing Endogenous RNA Network for Patients with Lung Adenocarcinoma

Abstract

Evidence is increasingly indicating that circular RNAs (circRNAs) are closely involved in tumorigenesis and cancer progression. However, the function and application of circRNAs in lung adenocarcinoma (LUAD) are still unknown. In this study, we constructed a circRNA-associated competitive endogenous RNA (ceRNA) network to investigate the regulatory mechanism of LUAD procession and further constructed a prognostic signature to predict overall survival for LUAD patients. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were selected to construct the ceRNA network. Based on the TargetScan prediction tool and Pearson correlation coefficient, we constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs, and 49 DEmRNAs. GO and KEGG enrichment indicated that the ceRNA network might be involved in the regulation of GTPase activity and endothelial cell differentiation. After removing the discrete points, a PPI network containing 12 DEmRNAs was constructed. Univariate Cox regression analysis showed that three DEmRNAs were significantly associated with overall survival. Therefore, we constructed a three-gene prognostic signature for LUAD patients using the LASSO method in the TCGA-LUAD training cohort. By applying the signature, patients could be categorized into the high-risk or low-risk subgroups with significant survival differences (HR: 1.62, 95% CI: 1.12-2.35, log-rank p = 0.009 ). The prognostic performance was confirmed in an independent GEO cohort (GSE42127, HR: 2.59, 95% CI: 1.32-5.10, log-rank p = 0.004 ). Multivariate Cox regression analysis proved that the three-gene signature was an independent prognostic factor. Combining the three-gene signature with clinical characters, a nomogram was constructed. The primary and external verification C -indexes were 0.717 and 0.716, respectively. The calibration curves for the probability of 3- and 5-year OS showed significant agreement between nomogram predictions and actual observations. Our findings provided a deeper understanding of the circRNA-associated ceRNA regulatory mechanism in LUAD pathogenesis and further constructed a useful prognostic signature to guide personalized treatment of LUAD patients.

Prognosis and Immunotherapy Response With a Novel Golgi Apparatus Signature-Based Formula in Lung Adenocarcinoma

“… Kim et al, 2019 ; Z. Li Y. et al, 2021 ; Perdrizet et al, 2021 ; Provencio et al, 2021 ; Yamaguchi et al, 2021 ). Erlotinib, the first approved target drug for NSCLC, is a reversible tyrosine kinase inhibitor that targets the epidermal growth factor receptor and can significantly improve the survival of LUAD patients ( Faehling et al, 2018 ).…”

Genome-wide analysis of circular RNAs and validation of hsa_circ_0086354 as a promising biomarker for early diagnosis of cerebral palsy

“…Further Pearson correlation was carried out to analyze the correlation between hsa_circ_0086354 and miRNAs, only interactions with significant negative correlation was retained. The circRNAs-miRNAs network was visualized by Cytoscape software (version 3.7.0; http://www.cytoscape.org ) [ 26 ].…”

Activation of circ_0072088/miR‐1261/PIK3CA pathway accelerates lung adenocarcinoma progression

“…[7][8][9] Recently, new evidence has shown that circRNAs participate in the initiation and development of LUAD. [10][11][12] Through bioinformatic analysis and literature reviews, [13][14][15] the consistent upregulation of circ 0072088 expression in LUAD has persuaded us to further examine its role. Paradoxically, some reports have shown that the downregulation of circ 0072088 in hepatic carcinoma cells derived exosome is associated with tumorigenesis, 16 similarly, its decrease has been reported to be associated with metastasis of colorectal cancer, 17 suggesting that, it is necessary to further explore the expression and function of circ 0072088 in the mechanisms underlying LUAD.…”

“…Studies have shown that circRNAs, which mainly function as molecular sponge by absorbing microRNAs and affecting gene expression, are involved in tumorigenesis and deterioration 7–9 . Recently, new evidence has shown that circRNAs participate in the initiation and development of LUAD 10–12 . Through bioinformatic analysis and literature reviews, 13–15 the consistent upregulation of circ 0072088 expression in LUAD has persuaded us to further examine its role.…”