RESUMO
BACKGROUND: Recent diagnostic procedure advances have greatly improved early lung cancer detection. However, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their application. There is a great need of novel non-invasive biomarkers for early lung cancer diagnosis. In the present study, we intend to determine whether the blood signatures of p14ARF promoter methylation are suitable for early detection of lung cancer. METHODS: The study aimed to assess the probability of p14ARF promoter methylation in plasma samples to detect early lung cancer using nested methylation-specific PCR in the training set consisted of tumor tissues and paired blood. Besides, we were further to discuss the difference in time to progression between methylation and unmethylation of p14ARF promoter using univariate and multivariate analysis. RESULTS: The methylation of p14ARF promoter was detected in 33.6 % of tumor tissues, and 12.1 and 25.2 % in distant-cancer mucosa and matched plasma, respectively, and our study has also demonstrated the positive correlation between them by Pearson's test (r = 0.300). The tumor-free survival time of the unmethylation of p14ARF promoter is significantly longer than that of the methylation of p14ARF promoter in tumor tissues (χ (2) = 7.149, P = 0.008). CONCLUSION: The methylation of p14ARF promoter in plasma samples has strong potential as a novel non-invasive biomarker for early detection of lung cancer, and the methylation of p14ARF promoter was considered as prognostic factor in our study.
Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Metilação de DNA , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas/genética , Proteína Supressora de Tumor p14ARF/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Taxa de Sobrevida , Proteína Supressora de Tumor p14ARF/sangueRESUMO
BACKGROUND AND AIMS: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. As CUGBP1 may also play a great role in tumor genesis and deterioration, the purpose of this study was to detect the expression of CUGBP1 mRNA and CUGBP1 and assess the prognostic significance of CUGBP1 in NSCLC. METHODS: Expression of CUGBP1 mRNA and CUGBP was detected by Semi-quantitative PCR and Immunohistochemistry, respectively, from 57 NSCLC patients. The percentage of CUGBP1 mRNA and CUGBP1 expression was correlated with clinical characteristics using χ (2) test. The prognostic significance was assessed by univariate and multivariate analyses in the Cox hazard model. RESULTS: The expression of CUGBP1 mRNA and CUGBP1 was over-expressed in cancer group and was correlated with TNM stage and Differentiation. By both univariate and multivariate survival analyses, CUGBP1 expression (P = 0.0074, HR = 3.701, 95 % CI 1.420-9.648), TNM-stage (HR = 4.043, 95 % CI 2.098-7.794) and age (HR = 3.207, 95 % CI 1.544-6.664) were noted to be independent indicators of a shorter postsurgical survival. CONCLUSIONS: The expression of CUGBP1 independently predicted a shorter postsurgical survival in NSCLC.
Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Proteínas de Ligação a RNA/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Proteínas CELF1 , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Diferenciação Celular , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
PURPOSE: Current knowledge of the prognostic biomarkers of advanced non-small cell lung cancer (NSCLC) treated with gefitinib is poor. NSE mRNA as a potential prognostic biomarker of the effectiveness of gefitinib treatment in NSCLC, especially in the Chinese population, needs to be further validated. PATIENTS AND METHODS: We retrospectively reviewed 168 advanced NSCLC patients treated with gefitinib between May 2006 and July 2010. NSE mRNA was measured using quantitative RT-PCR analysis for correlation with the clinical outcomes. RESULTS: We found that NSE mRNA expression was inversely correlated with sensitivity to gefitinib in NSCLC patients. Patients without elevated NSE mRNA had a more RR (CR + RR) 45.1 % than elevated 18.9 % (P = 0.0005). Moreover, the time to progression was 6.0 versus 4.2 months, respectively. Log-rank test was marginally significant (χ(2) = 12.11, P = 0.0007) and Cox multivariate analysis revealed that NSE mRNA (HR = 3.076; 95 % CI 1.943-4.870; P < 0.0001) was an independent prognostic factor of NSCLC patients in the Chinese population. CONCLUSION: For NSCLC patients treated with gefitinib, patients without elevated NSE mRNA had a better prognosis than those with elevated NSE mRNA. Pretreatment NSE mRNA holds great potential as a prognostic biomarker in advanced NSCLC. Therefore, it is proposed that NSE mRNA should be routinely detected to screen patients who are more likely to benefit from gefitinib-based treatment.