Prognostic Factors Of Early Postoperative Lung Adenocarcinoma

Objectives:Patients with pathological stage I lung adenocarcinoma show variabilities in prognosis even after complete resection.The factors resulting in heterogeneities of prognosis remain controversy.The aim of this study was to identify the risk factors affecting recurrence/metastasis and survival in patients with curatively resected p I lung adenocarcinoma.Methods:252 patients with p I lung adenocarcinoma were retrospectively reviewed in order to analyze the associations of recurrence and survival with following clinicopathological variables:gender,age,smoking cigarette,family cancer history,tumor size,TNM stage,tumor differentiation,visceral pleural invasion,bronchial involvement,lymphovascular invasion,numbers of resected lymph nodes,postoperative adjuvant treatment,pathological sub-types.SPSS(V22.0,SPSS)was used for statistical analysis.DFS and OS curves were estimated using the Kaplan-Meier method.Significance was assessed using the log rank test.A P-value of<0.05 was considered statistically significant.Possible prognostic predictors of DFS and OS were analyzed using Cox univariate and multivariate proportional hazards regression.Results:Among those 252 patients,48(19.1%)had local recurrence or distant metastasis,the rest 204 patients had no relapse until the last follow-up.Cox univariate survival analysis revealed that tumor size,TNM stage,tumor differentiation,bronchial involvement,lymphovascular invasion and micropapillary component were significantly associated with disease-free survival(DFS)and overall survival(OS),while smoking cigarette were found to be a risk factor for DFS either.In multivariate analysis,tumor differentiation,bronchial involvement,lymphovascular invasion and micropapillary component were independent risk factors for DFS and OS,while TNM stage was proved to be a significant factor only for DFS.Kaplan-Meier analysis established that tumor size,TNM stage,tumor differentiation,bronchial involvement,lymphovascular invasion,pathological subtype and micropapillary component were factors that significantly correlated with survival.Conclusions:tumor differentiation,bronchial involvement,lymphovascular invasion and micropapillary component could be considered as risk factors for predicting local recurrence or distant metastasis and survival in curatively resected p I lung adenocarcinoma patients.MiRNAs are reported to be involved in crucial biological processes,including cellular development,differentiation,apoptosis and proliferation,through imperfect pairing with target messenger RNAs(mRNAs)of protein-coding genes and the transcriptional or post-transcriptional regulation of their expression.Changes in the expression level of miRNAs have subsequently been detected by different groups in many types of human tumours.MicroRNA alterations are involved in the initiation and progression of human cancer.MiRNA expression profiling of human tumours has identified signatures associated with diagnosis,staging,progression,prognosis and response to treatment.5-year survival rate of lung adenocarcinoma patients with stage IA and IB can reach more than 70%,however,some early lung cancer patients will still suffer from occur recurrence and/or remote metastasis death within two years.There are few studies report on the characteristic miRNA expression profiles and differentially expressed miRNAs associated with recurrence and/or metastasis.The aim of this study was to search for the miRNA expression difference between the above two groups.In this study,analysis of DNA microarrays-based miRNA expression profiles of lung adenocarcinoma was performed in formalin-fixed and paraffin-embedded(FFPE)tissues blocks,to screen out the characteristic miRNA expression profiles and to identify the differentially expressed miRNAs associated with recurrence and metastasis.80 FFPE tissues blocks were divided in two groups:Group 1,having recurrence and/or metastasis within 2 years;Group 2,no recurrence and/or metastasis within ? 5 years.The total RNAs were prepared from the FFPE blocks derived from 80 FFPE tissues blocks,and then hybridized with the Agilent Human miRNA microarrays.The microarray data was processed with softwares,including GeneSpring GX,R-Project,etc.Based on bioinformaticaI analysis,the miRNA expression profiles were obtained.Through comparing data of the group 1 with group2,6 miRNAs with significantly different expression(p<0.05)between two groups and associated with recurrence and metastasis were identified:including.miR-3651?miR-183-5p?miR-4685-5p?miR-4453?miR-6511a-5p? miR-3692-5p.Among of them,miR-3651 was found to be significantly expressed in the group without recurrence and miR-183-5p?miR-4685-5p?miR-4453?miR-6511a-5p? miR-3692-5p in the group with recurrence.The above 6 miRNAs were submitted to on TargetScan website in order to find the 100 selected target genes,then 100 target genes were submitted to DAVID database to identify the significant biological functions.Based on the data,6 miRNAs were correlated with cell circle,cell immigration,cell apotosis and signal transduction,which revealed that 6 miRNAs may play an important role in the development of tumor and recurrence/metastasis.In conclusion,a panel of significantly and differently expressed miRNAs(miR-3651?miR-183-5p?miR-4685-5p?miR-4453?miR-6511a-5p?miR-3692-5p)derived from the miRNA expression profile may serve as the potential molecular biomarkers for the prediction of recurrence and metastasis as well as adjuvant therapy in early lung adenocarcinoma.