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• W4251237545 abstract "Abstract Background : Circadian rhythm plays an influential role in the vast majority of behavior and physiology, even of tumorigenesis and development. In this study, we tried to explore the prognostic implication for non-small cell lung cancer (NSCLC) based on the expression profiles of circadian clock-related genes (CCRGs), and describe the changes of immune infiltration and cell functions of related to the circadian rhythm. Methods : Univariate and multivariate Cox proportional hazard regression were performed to determine and construct a CCRGs risk-score significantly correlated with overall survival (OS) of the training set and validation set. GO, KEGG, and GSVA indicated discrepant changes in cellular processes and signaling pathways associated with these CCRGs. Further, immune cell infiltration, mutation rates, and related drugs and pathways analyses were investigated by the online analysis platform and the algorithm provided by works of literature. Results : The risk-score based on ten-gene signatures could independently predict the OS both in TCGA lung adenocarcinoma (p < 0.0001, HR: 2.117, 95% CI: 1.546 to 2.900) and lung squamous cell carcinoma (p < 0.0001, HR: 2.066, 95% CI: 1.552 to 2.751), respectively. The risk-score also had superior accuracy and predictability (LUAD: AUC 0.788; LUSC: AUC 0.738). The prognostic performance of the ten-gene signature was finally validated in validation set based on GEO cohorts. The circadian oscillations driven by CCRGs could disturb the metabolism and cellular functions of cancer cells. We also found that the infiltration level of critical cells in specific anti-tumor immunity process was suppressed apparently. In contrast, the infiltrating of inflammatory cells and immune cells with negative regulatory effects were promoted in the high-risk group. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets. Conclusions: We described the landscapes and prognostic implications of CCRGs. The risk-score based on CCRGs was an independent predictor of prognosis and could significantly stratify patient outcomes and immune cell infiltration levels. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets. Our study revealed that circadian rhythms might play an influential role in the NSCLC." @default.
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• W4251237545 date "2020-06-17" @default.
• W4251237545 modified "2023-09-28" @default.
• W4251237545 title "Genetic Landscapes and Prognostic Implications of Circadian rhythm in Non-small Cell Lung Cancer" @default.
• W4251237545 doi "https://doi.org/10.21203/rs.3.rs-35737/v1" @default.
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