ABSTRACT
Objective To explore the prognostic significance of nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-6 (SIRT6), encoded by the sirtuin 6 ( SIRT6) gene, in a population of Chinese Han patients with non-small cell lung cancer (NSCLC). Methods Cancer tissues and normal lung tissues (>5 cm adjacent to cancer tissue) were collected from Chinese Han patients with NSCLC. Expression levels of SIRT6 and histone H3-acetyl K56 ( H3K56), in cancer and normal lung tissues from patients with NSCLC, were detected by reverse-transcription polymerase chain reaction, Western blot and immunohistochemistry. Correlations between SIRT6 expression and various clinicopathologic features were investigated. Results Out of 86 patients included in the study, mRNA and protein SIRT6 levels were down-regulated in NSCLC tissue versus normal lung tissue, and SIRT6 levels were inversely correlated with H3K56 levels. Positive rates of SIRT6 were significantly correlated with degree of cell differentiation, TNM stage, lymph node metastasis, overall survival and metastasis-free survival. Conclusion Downregulation of SIRT6 expression may promote NSCLC malignancy in the Chinese Han population. SIRT6 may be a potential therapeutic target in Chinese Han patients with NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Down-Regulation/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Sirtuins/genetics , Aged , Asian People/genetics , Disease-Free Survival , Ethnicity/genetics , Female , Gene Expression Regulation, Neoplastic , Histones/metabolism , Humans , Kaplan-Meier Estimate , Lysine/metabolism , Male , Middle Aged , NAD/metabolism , Neoplasm Metastasis , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sirtuins/metabolism , Survival AnalysisABSTRACT
BACKGROUND: To evaluate the clinical efficacy and toxicity of GP (gemcitabine+cisplatin) and NP (navelbine+cisplatin) regimens in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Seventy-six cases of advanced NSCLC were enrolled. Among them, 36 received GP (gemcitabine 1.0 g/m² D1,8,15+cisplatin 30 mg/m² D1-3), meanwhile 40 were administrated NP regimen (navelbine 30 mg/m² D1,8+cisplatin 30 mg/m² D1-3). RESULTS: The overall response rates of GP and NP were 52.8% and 47.5% respectively (P > 0.05), and the median survivals were 9.8 and 8.7 months respectively (P > 0.05). The main toxicity was hematological toxicity. The incidences of leukopenia were 58.3% and 92.5% in GP and NP respectively (P < 0.01), and those of grade III-IV leukopenia were 16.7% and 52.5% respectively (P < 0.01 ). There was no significant difference in thrombocytopenia incidence between the two groups, however, GP group had a remarkably higher incidence of grade III-IV thrombocytopenia (33.3%) than NP group ( 10.0% ) (P < 0.05 ). CONCLUSIONS: Efficacy of GP regimen is similar to that of NP and both of them can be well tolerated by patients.