| The research backgroundDiffuse intrinsic pontineglioma(DIPGforshort)is a highly invasive glioma,the brainstem and much in childhood onset,incidence of pediatric brain and central nervous system tumors account for about 10% ~ 15%,also can bedirectly called diffuse endogenous pons glioma in children.Since 1926,Harris and Newcomb reported the first case occur in children pons diffuse invasive glioma,people around the DIPG from observation,analysis,diagnosis,treatment and future solutions for nearly a century of clinical practice and theory research,and obtained a series of significant results.The current treatment practices about DIPG usually first by observing the patients clinical manifestation,imaging findings andcorresponding pathological analysis to the differential diagnosis of patients,and then through the mainstream of chemotherapy to the affected areas,supplemented by radioactive therapy coordinating role,is for prognosis after observation and nursing care.In practice,however,DIPG has a poor prognosis,with less than 10 percent of the children surviving for more than two years.The incidence of DIPG was mainly in school-age and preschool children,and MRI was typical.For most DIPG cases,radiotherapy as a palliative intervention can temporarily improve clinical symptoms.However,tumor progression is almost inevitable.The median survival period is 8 ~ 11 months,and the overall survival rate is about 30% in 1 year,and less than 10% of cases can reach 2 years.Only 2 to 3 percent of cases have long-term survival,and these cases tend to have atypical MRI findings and clinical symptoms.There have been more than 200 clinical trials in the world,including radiotherapy and cytotoxic chemotherapy,but no breakthrough has been made in the treatment of the initial or recurrent DIPG.DIPG's research has stalled because of the lack of biopsies in DIPG.The imaging manifestations of DIPG are very typical.Biopsy is performed only in atypical cases,and few tissue specimens before treatment have limited the molecular biology of the disease.Surgery and molecular analysis technology in recent years progress by leaps and bounds,biopsy,greatly improve the safety of the brainstem biopsy applied gradually in many clinical trials,DIPG molecular pathology and treatment will make new breakthrough.The scholarly research on diffuse endogenous pons glioma,scholars at home and abroad,from the Angle of biology,pathology,chemistry,etc,the clinical manifestation,pathological identification of DIPG,pathogenesis,treatment and so on have rich and in-depth exploration,and achieved fruitful results.And search through all kinds of information about the academic and literature,research on diffuse brain gliomas prognosis factors of endogenous bridge and possible pathogenesis have been no major breakthroughs were made in the research field,so no matter from the necessity of the research topics and depth,can have development space.Based on the above,the necessity of the need of clinical practice and academic research,this thesis children diffuse brain gliomas prognosis related factors of endogenous bridge exploratory analysis,as well as the possibility of the pathogenesis of a detailed discussion.The first chapter of this study on the endogenous bridge with glioma patients treated in our clinical and follow-up data were retrospectively studied,filter to obtain relatively objective data and past literature exists in the controversial clinical and therapeutic factors,including age,sex,duration of symptoms,preoperative KPS score,pathologic stage,postoperative radiotherapy,chemotherapy and other statistical analysis.To explore the relationship between different clinical factors and different treatment methods and the prognosis of patients with diffuse endogenous bridge glioma,and to explore the reasons for the effect of various factors on the prognosis.Second Zhang Cai using reverse transcription polymerase chain(reverse transcription polymerase chain reaction,RT-PCR)method in the detection of tumor tissue of micrornas-210,the mi RNA-125-B,phosphatidyl inositol 3 kinase(phosphatidylinositol 3 kinase,PI3K),protein kinase B(protein kinase B,PKB,AKT)mRNA expression level,discusses their relationship with the pathological grading and prognosis.In order to better judge the prognosis of patients with diffuse endogenous brain bridge glioma and to adopt more effective and more targeted treatment plan for patients with different glioma.Help for the diffuse of compatriots endogenous pons glioma standardized treatment as soon as possible,make numerous diffuse endogenous pons glioma patients can get right in the existing medical conditions and standard treatment.ObjectiveFirst,to retrospectively analyze the characteristics and clinical data of Diffuse Intrinsic Pontine Glioma(DIPG)in 33 children and find out the related factors that affect its prognosis.Second,to detect the expression of mi RNA-210,mi RNA-125 b,and PI3 K / AKT in tumor tissue and to provide a theoretical basis for the pathogenesis of DIPG.MethodPart ?: The data of patients with DIPG from December 2006 to July 2017 in our hospital were collected,including the gender,time of onset,WHO classification of central nervous system tumor,KPS score,treatment,H3K27 M test results and life time.First,the overall survival rate of children was analyzed,and then the factors was analyzed by Kaplan-Meier single factor survival analysis and multivariate Cox regression analysis.Part ?: Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression of mi RNA-210,mi RNA-125 b,phosphatidylinositol-3 kinase(PI3K)B protein kinase B(PKB,AKT)m RNA expression levels.The differences of mi RNA-210,mi RNA-125 b,PI3K and AKT expression between tumor tissues and adjacent tissues were compared by t test.The expression of mi RNA-210,mi RNA-125 b,PI3K,AKT and survival were analyzed by Kaplan-Meier single-The relationship between the expression levels of mi RNA-210,mi RNA-125 b,PI3K and AKT in WHO grade was analyzed by Spearman rank correlation analysis.Pearson correlation analysis was used to analyze the correlation between the expression of mi RNA-210 and mi RNA-125 b in PI3 K and AKT.ResultPart ?: In 33 cases of DIPG patients,18 males,accounting for 54.55%,15 females,accounting for 45.45%.The incidence of age range of 23 to 145 months,the median age was 72 months.WHO ? grade in 6 cases,WHO ? grade in 8 cases,WHO ? ~ ? grade in 10 cases,WHO ? grade in 7 cases,WHO ? grade in 2 cases.KPS score range of 50 to 80 points,the median was 60 points.24 cases were positive in H3K27 M test,9 cases were negative in H3K27 M test.The median survival time was 6.88 months.As of the study,a total of 28 patients died with a mortality rate of 84.85%.The Kaplan-Meier analysis showed that there was no significant difference in survival between sex groups(?2 = 0.001,P = 0.980).There was no significant difference in survival between age groups(?2 = 0.203,P = 0.652)There were significant differences in survival between the WHO grade groups(?2 = 21.613,P = 0.000).There was significant difference in survival between the KPS score groups(?2 = 24.311,P = 0.000).There was no significant difference in survival between radiotherapy groups(?2 = 0.504,P = 0.478).There was no significant difference in survival between chemotherapy groups(?2 = 0.000,P = 0.990).There was significant difference in survival between H3K27 M test groups(?2 = 5.243,P = 0.022).Cox multivariate analysis showed that KPS scores and H3K27 M results were independent risk factors for the survival time of patients with DIPG(P = 0.027,0.000).Part ?: The expression of mi RNA-210,mi RNA-125 b,PI3K and AKT in 27 cases of tumor tissues were higher than that in paracancerous tissues,the difference was statistically significant(P <0.05).The median expression of mi RNA-210 in tumor tissue was 7.36,the median of mi RNA-125 b expression was 7.11,the median of PI3 K expression was 10.18,and the median of AKT expression was 7.91.The Kaplan-Meier analysis showed that the difference of survival between high expression group and low expression group was statistically significant(?2 = 19.250,P = 0.000).Spearman rank correlation analysis showed that the correlation coefficient between mi RNA-210 and DIPG WHO was 0.382,P = 0.049.The correlation coefficient between mi RNA-125 b and DIPG WHO was 0.423,P = 0.028.Pearson correlation analysis showed that there was a positive correlation between the expression of mi RNA-125 b and PI3 K and AKT in tumor tissues,the correlation coefficients were 0.697,0.765 respectively,with statistical significance(P = 0.000).There was a positive correlation between the expression of mi RNA-125 b and PI3 K and AKT in tumor tissues,the correlation coefficients were 0.697,0.765 respectively,with statistical significance(P = 0.000).ConclusionKPS score and H3K27 M results in children with DIPG are independent risk factors for survival time.The expression of mi RNA-210 and mi RNA-125 b in tumor tissue is a risk factor of survival time.And the expression of mi RNA-210 and mi RNA-125 b is positively correlated with the classification of DIPG,PI3 K and AKT.mi RNA-210,mi RNA-125 b may play a role in the development of DIPG by regulating the expression of PI3 K and AKT in tumor tissues. |
PDF Full Text Request