Associations of sirtuins with clinicopathological parameters and prognosis in non–small cell lung cancer

Abstract

Background: Lung cancer is the leading cause of cancer-related death worldwide and it is critical to discover specific biomarkers to provide better individualized treatment and subsequently better prognosis. The sirtuins (SIRT1–7) have been reported to be involved in cancers including non-small cell lung cancer (NCSLC), however, the results are not consistent and not all the seven sirtuins are explored and compared. Methods: TCGA data was downloaded and used to investigate and compare the associations of sirtuins mRNA levels with clinicopathological parameters and prognosis in NSCLC. Results: Our results suggested SIRT1, SIRT3, SIRT4, and SIRT7 were highly expressed in adenocarcinoma (ADC) patients and female patients while SIRT5 were highly expressed in squamous cell carcinoma (SCC) patients and male patients. Associations of high SIRT7 with younger onset age, high SIRT1 with distant metastasis and low T stage, and high SIRT4 with high T stage and TNM stage were also found. Kaplan-Meier plot curves and univariate Cox proportional regression analyses indicated that high SIRT2, SIRT4, and SIRT6 expressions were associated with longer overall survival (OS) time. Multivariate analyses indicated that SIRT2 and SIRT6 were still associated with OS. For recurrence-free survival (RFS), high SIRT1 expression was significantly associated with shorter RFS time while high SIRT2-3 and SIRT5-7 expressions were associated with longer RFS time in univariate analyses. After adjusting the confounding factors, significant associations were still found in SIRT1-2 and SIRT5-7 but not in SIRT3. We also stratified the patients by combining SIRT1 and SIRT2 and revealed that the combination of SIRT1 and SIRT2 was a better prediction model for RFS in NSCLC. To preliminarily understand the potential mechanisms of sirtuins in NSCLC carcinogenesis, the genes co-expressed with sirtuins were analyzed and annotated. Conclusion: sirtuins might be the potential therapy targets and prognostic biomarkers in NSCLC.