ABSTRACT
Purpose@#Most lung adenocarcinoma (LUAD) patients are diagnosed at the advanced stage and have poor prognosis. DNA methylation plays an important role in the prognosis prediction of cancers. The objective of this study was to identify new DNA methylation sites as biomarkers for LUAD prognosis. @*Materials and Methods@#We downloaded DNA methylation data from The Cancer Genome Atlas data portal. Cox proportional hazard regression model and random survival forest algorithm were applied to identify the DNA-methylation sites. Methylation of sites were validated in the Gene Expression Omnibus cohorts. Function annotation were done to explore the biological function of DNA methylated sites signature. @*Results@#Six DNA methylation sites were identified as prognosis signature. The signature yielded acceptable discrimination between the high-risk group and low-risk group. The discrimination effect of this DNA methylation signature for the OS was obvious, with a median OS of 21.89 months vs. 17.74 months for high-risk vs. low-risk groups. This prognostic prediction model was validated by the test group and GEO dataset. The predictive survival value was higher for the prognostic prediction model than that for the tumor node metastasis stage. Adjuvant hemotherapy could not affect the prediction of the signature. Functional analysis indicated that these signature genes were involved in protein binding and cytoplasm. @*Conclusion@#We identified the prognostic signature for LUAD by combining six DNA methylation sites. This could service as potential robust and specificity signature in the prognosis prediction of LUAD.
ABSTRACT
Objective To study the serum levels of progastrin-releasing peptide (pro-GRP) and neuron-specific enolase (NSE) for the clinical diagnosis,therapy monitoring and survival time analysis of small cell lung cancer (SCLC).Methods All 41 SCLC samples (30 males,11 females,age range from 46 to 78 years),95 NSCLC samples (55 males,40 females,age range from 42 to 88 years),and 127 normal individuals samples (80 males,47 females,age range from 35 to 78 years) which were diagnosed by People's Hospital of Zhengzhou from May 1,2008 to April 30,2011 were collected.Serum levels of pro-GRP,NSE and their changes in SCLC patients before and after therapy were evaluated.ANOVA analysis,randomized block design analysis of variance and the log-rank test were collected SPSS 16.0 to evaluate the survival time.Results The serum levels of pro-GRP (median 357.8 ng/L) and NSE (median 89.5 μg/L) in SCLC group were significantly higher than those in the NSCLC group (pro-GRP:39.9 ng/L;NSE:11.43 μg/L) and normal individuals group (pro-GRP:12.7 ng/L;NSE:10.03 μg/L) (P=0.000).The sensitivity of pro-GRP and NSE for the diagnosis of SCLC were 80.4％ and 78.0％,while the specificity were 92％ and 87％,respectively.There is a poor correlation between pro-GRP and NSE serum levels,but when combined the sensitivity can be 95％ and specificity can be 85％.Significantly statistical difference of pro-GRP levels was observed in the different stages of treatment (before and after therapy) in SCLC-LD patients (F =3.53,P =0.038),and significant statistical difference of NSE levels was also observed in SCLC-ED patients in different stages (F =16.049,P =0.000).In partied response SCLC patients,the group with NSE level lower than cut-off value had longer survival time than the other group with NSE level higher than cut-off value (P =0.001).Conclusions The sensitivity of the combined analysis of pro-GRP and NSE is better than single marker for the diagnosis of SCLC.The serum level of pro-GRP has better correlation with therapeutic effect of SCLC-LD patient than NSE.The serum level of NSE are well correlated with therapeutic effect in SCLC-ED patients.There are some certain value of NSE level for evaluation the survival time of SCLC patients who were in partial response.