Exploration of a Novel Circadian miRNA Pair Signature for Predicting Prognosis of Lung Adenocarcinoma

SIMPLE SUMMARY: Identifying new prognostic markers can provide a reference for the treatment of lung adenocarcinoma (LUAD) to improve its prognosis. Circadian rhythm disturbances are closely linked to the initiation, progression and prognosis of lung cancer. We aimed to explore the value of circadian miRNA (cmiRNA) as a prognostic marker of LUAD. A prognostic signature comprising seven pairs of cmiRNAs was established, and it exhibited excellent predictive value for overall and progression-free survival. High-risk patients showed higher sensitivity to primary chemotherapy drugs and targeted medicine compared with low-risk patients. Overall, the novel circadian-related miRNA pair signature could provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for LUAD. The cmiRNA–Cgenes network and corresponding enrichment analysis might provide clues for studying the underlying circadian dysregulation mechanisms involved in the progression of LUAD in the future. ABSTRACT: Lung adenocarcinoma (LUAD) is the primary histological subtype of lung cancer with a markedly heterogeneous prognosis. Therefore, there is an urgent need to identify optimal prognostic biomarkers. We aimed to explore the value of the circadian miRNA (cmiRNA) pair in predicting prognosis and guiding the treatment of LUAD. We first retrieved circadian genes (Cgenes) from the CGDB database, based on which cmiRNAs were predicted using the miRDB and mirDIP databases. The sequencing data of Cgenes and cmiRNAs were retrieved from TCGA and GEO databases. Two random cmiRNAs were matched to a single cmiRNA pair. Finally, univariate Cox proportional hazard analysis, LASSO regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature consisting of seven cmiRNA pairs. The signature exhibited good performance in predicting the overall and progression-free survival. Patients in the high-risk group also showed lower IC50 values for several common chemotherapy and targeted medicines. In addition, we constructed a cmiRNA–Cgenes network and performed a corresponding Gene Ontology and Gene Set enrichment analysis. In conclusion, the novel circadian-related miRNA pair signature could provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for LUAD.