| PART?.Long noncoding RNA expression profiling by microarray in diffuse large B cell lymphoma and preliminary bioinformatics studyObjective: Application of high-throughput genomics technology to analysis the differences in lnc RNA/m RNA expression profiles between the patients with diffuse large B cell lymphoma?DLBCL?and reactive hyperplasia of lymph node?RLN?,and between different disease states of DLBCL,in order to explore the role of the aberrantly expressed lnc RNAs in the pathogenesis of DLBCL.Materials and methods: Tumor tissue samples from five newly diagnosed DLBCL,3 relapsed DLBCL patients and 4 samples of RLN were collected.SBC-lnc RNA human 4x180k)chip was used to profile expression of lnc RNA/m RNAs.Bioinformatics methods were performed for data analysis,including screening of differentially expressed lnc RNA/m RNAs,gene ontology?GO?and KEGG pathway enrichment analysis,and lnc RNA/m RNA co-expression network construction,etc.Portion of dysregulated lnc RNAs from the microarray data analysis was selected for validation using quantitative real-time polymerase chain reaction?q RT-PCR?.Results:?1?In patients with newly diagnosed DLBCL,compared with RLN,5,806 dysregulated lnc RNAs were found.Among these,2,650 lnc RNAs were significantly upregulated,while 3,156 lnc RNAs were significantly downregulated.From the m RNA expression profiling data,5,628 differently expressed m RNAs were found.Among them,2,045 were significantly upregulated and 3,583 downregulated.The most enriched GO targeted by dysregulated transcripts were involved in detection of chemical stimulus involved in sensory perception of smell,olfactory receptor activity,G-protein coupled receptor activity,mitotic cell cycle and extracellular matrix.KEGG pathway analysis showed that 42 pathways and the most enriched network correlated with tumor was the “cell cycle”.The coding and non-coding gene expression network construction showed the significantly correlation between lnc-FAM27B-22:1 and m RNAs,including CDCA7 L,CEBPB,CHRDL1 and SMIM9.We speculated that lnc-FAM27B-22:1 might have a critical function in pathogenesis of DLBCL.Forteen lnc RNAs were validated in the same sample series and the results showed the similar changing trend with that of the microarray results.?2?In patients with primary refractory DLBCL,compared with chemo-sensitive patients,425 dysregulated lnc RNAs were found.Among these,124 lnc RNAs were significantly upregulated,while 301 lnc RNAs were significantly downregulated.From the m RNA expression profiling data,251 differently expressed m RNAs were found.Among them,90 were significantly upregulated and 106 downregulated.The most enriched GO targeted by dysregulated transcripts were involved in detection of chemical stimulus involved in immune system process,cell activation and somatic diversification of immune receptors.KEGG pathway analysis showed that 25 pathways and the most enriched network correlated with tumor was the “cell adhesion molecules”.?3?In patients with relapsed DLBCL,compared with newly diagnosed patients,605 dysregulated lnc RNAs were found.Among these,169 lnc RNAs were significantly upregulated,while 436 lnc RNAs were significantly downregulated.From the m RNA expression profiling data,365 differently expressed m RNAs were found.Among them,201 were significantly upregulated and 164 downregulated.The most enriched GO targeted by dysregulated transcripts were involved in detection of chemical stimulus involved in cell morphogenesis and necroptotic process.KEGG pathway analysis showed that 24 pathways and the most enriched network correlated with tumor was the “Glycosaminoglycan biosynthesis-keratan sulfate”.?4?Fourteen dysregulated lnc RNAs expressions were analyzed using q RT-PCR to validate the microarray analysis results.In all but one lnc RNA,consistent trend of expression changes was observed in two methods.Conclusions: In patients with newly diagnosed DLBCL versus RLN,and between different disease states of DLBCL,the lnc RNA/m RNA expression profiles were significantly altered.Differentially expressed m RNAs are involved in a number of biological functions and signaling pathways.It prompt lnc RNA may play an important role in the mechanism of occurrence,drug resistance and relapse of DLBCL.The above results provide the theory basis for the further study on the role of differentially expressed lnc RNA in the development of DLBCL and its potential application as the possible biomarkers of early diagnosis and prognosis.PART? Correlation of 18F-FDG-PET/CT with clinical factors and prognosis in patients with newly diagnosed diffuse large B-cell lymphomaObjectives: The aim of this study is to determine the correlation of pretreatment,interim and post-treatment 18F-fluoro-2-deoxy-D-glucose positron-emission tomography/ computed tomography?PET/CT?with clinicopathological factors and its prognostic value in patients with newly diagnosed diffuse large B-cell lymphoma?DLBCL?.Patients and methods: A single center,open-label clinical study was conducted.The patients received R-CHOP or CHOP regimen as the first-line therapy.PET/CT scans were performed before therapy?PET0?,after third cycle?interim scan,PET3?and sixth cycle of chemotherapy?post-treatment scan,PET6?.The PET/CT was assessed by three criteria: International Harmonization Project?IHP?criteria,the Deauville five-point scale?5-PS?and ?SUVmax.The relationship of pretreatment SUVmax with clinicopathological factors and efficacy were evaluated.The value of PET/CT in predicting progression-free survival?PFS?and overall survival?OS?were analyzed.Results:?1?A cohort of 140 patients with newly diagnosed DLBCL who had undergone pretreatment PET/CT were enrolled.Pretreatment SUVmax between groups significantly differed with respect to each of International Prognostic Index?IPI?factors,except for age and performance status.High SUVmax was associated with high Ki-67 and Glut-3 protein expression,but not with Glut-1.Complete remission rate was differed significantly between the low?SUVmax?9.0?and high SUVmax?SUVmax>9.0?groups?91.7% vs.61.1%,P<0.001?.Patients with low SUVmax showed favorable survival?3-year PFS: 92.2% vs.63.6%,P<0.001;3-year OS: 95.5% vs.78.3%,P=0.003?.On multivariate analyses,SUVmax predicted PFS independent of Revised-IPI?SUVmax: P=0.011,HR 4.784;Revised-IPI: P=0.004,HR 2.551?.Then a novel prognostic model was established by combining the IPI score and the pretreatment SUVmax value.?2?Of 140 patients with newly diagnosed DLBCL,69 patients received interim PET/CT scan.The results showed that 5PS and ?SUVmax was more efficient than IHP criteria in predicting disease progression and death.On multivariate analyses,5PS>3 and ?SUVmax<80% in interim PET/CT independently predicted PFS and OS.A novel interim prognostic model was established by combining the IPI score,the pretreatment SUVmax value and interim PET/CT result.?3?Of 140 patients with newly diagnosed DLBCL,73 patients received post-treatment PET/CT scan.The results showed that 5PS was more efficient than IHP criteria and ?SUVmax in predicting disease progression and death.On multivariate analyses,5PS>3 in post-treatment PET/CT independently predicted PFS and OS.Conclusion: Pretreatment,interim and post-treatment PET/CT scan can effectively predict the survival outcome in patients with DLBCL.A novel prognostic model based on IPI score/pretreatment SUVmax might be useful for risk stratification of patients with newly diagnosed DLBCL. |
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