Expression Of PTEN And Beclin-1 In Children With Non-Hodgkin’s Lymphoma And Its Significance

Objective: Lymphoma is one of the most common malignant diseases occurs in children.After leukaemia and brain neoplasm,lymphoma ranks the third in children’s malignant tumor,many of these will be highly invasive form of non-Hodgkin lymphoma.In recent years,with the continuous improvement of the traditional chemotherapy regimens,maturity of hematopoietic stem cell transplantation,the appearance of cancer immunotherapy and gene targeting drugs,5 years event-free survival of chidlren with NHL can reaches 70%-90% if they get correct diagnosis,classification and timely treatment.However,the treatment failed in some children,because of drug resistance,the primary disease progression and recurrence,while the side effects of traditional chemotherapy can not be ignored,looking for new effective drugs is the key to improve prognosis.PTEN is a tumor suppressor gene,researches show that PTEN can suppress proliferation,accelerate cell apoptosis,inhibit angiogenesis by means of multiple pathways.Downregulating PI3K/Akt signaling pathway is the main role of PTEN.PI3K/Akt signaling pathway is aberrantly activated and play a important role in carcinoma in a variety of tumors including NHL.Studies found that the deletion of PTEN occurred in endometrial cancer,thyroid cancer,ovarian cancer,gastric carcinoma,glioma,adult lymphoma and so on.Autophagy can degrade long-lived proteins and cytoplasmic organelles by using lysosome,so that the cells can suit their own metabolic requirements and complete the updating of organelle.Autophagy is an evolutionarily conserved cellular defence mechanisms,again is a mechanism of programmed cell death.In recent years,studies about the relationship of autophagy and tumors have become focous gradually.Autophagy related gene beclin-1 can up-regulate autophagy,it combined with PI3 K and plays a key role in the formation of autophagosome.Many studies have shown that autophagy exhibited antitumor activity and beclin-1 was a tumor-suppressor gene.ClassⅠPI3K can suppress autophagy activity,while PTEN can down-regulate ClassⅠPI3K/AKT pathway,so promote autophagy.Currently,researches about the expression of PTEN and Beclin-1 in children’s NHL are extremely rare domestic and overseas.Our aim is to explore the function of the two kinds of tumor suppressor genes in children’s NHL through detecting the expression of protein PTEN and Beclin-1 and analysing their correlations with clinicopathologic features as well as determining the relation between them.Methods:The paraffin-embedded tissues came from 36 children with NHL were classified into experimental group,these children were confirmed by pathological diagnosis after resection or biopsy and they came from the Pediatrics of The Fourth Hospital of Hebei Medical University from January 2008 to May 2015.Among the children,there were 24 boys and 12 girls,14 cases were 7 years old or younger,and 22 cases were more than 7 years old,According to immunophenotyping,20 cases were T type,16 cases were B type,according to the St.Jude non-Hodgkin’s lymphoma staging system,6 cases were Ⅱ or stage Ⅲand 30 cases were Ⅳstage,24 cases had elevated LDH level,12 cases had normal LDH level,acording to IPI,15 cases were lower risk group,21 cases were higher risk group,21 cases had lower Ki-67(≤80%),15 cases had higher Ki-67(> 80%).Another 26 paraffinembedded tissues of children with lymph node reactive hyperplasia were used as control group.Immunohistochemical S-P method was employed to detect the expression of PTEN protein and Beclin-1 protein.The two proteins’ correlations with clinicopathologic features as well as the relation between themselves were further researched.The data was then analysed by SPSS 13.0 software package.Count data was analysed by χ2test,the method of Spearman was used to study the corrlation.Inspection standard a=0.05.Results:1 The positive rate of PTEN in tissues from 36 children with NHL and 26 children with RH were 47.2% and 80.8% respectively,the diffrence is statistically significant(χ2=7.161,P<0.05).Comparing the expression in different groups,we found that the positive rate of PTEN in lower-risk group was quite higher than that in higher-risk group,the diffrence is statistically significant(χ2=11.085,P<0.05).The positive rate in LDH normal group was quite higher than that in elevated group,the diffrence is statistically significant(χ2=5.573,P<0.05),but the expression of PTEN was not related to patients’ gender,age,immunophenotype,clinical staging,B symptoms and the expression of Ki-67(P>0.05).2 The positive rate of Beclin-1 in tissues from 36 children with NHL and 26 children with RH were 50% and 84.6% respectively,the diffrence is statistically significant(χ2=7.902,P<0.05).The expression of Beclin-1 was not related to patients’ gender,age,immunophenotype,clinical staging,serum LDH,B symptoms,the expression of Ki-67 and IPI in children with NHL(P>0.05).3 A significantly positive correlation was discovered between the expression of PTEN and Beclin-1 in children with NHL(r=0.501,P <0.05).Conclusions:1 The positive rate of PTEN protein was significantly decreased in children with NHL and the expression of PTEN protein was related to IPI and LDH level,namely higher risk and elevated LDH often accompanied with decreased expression of PTEN protein.This reminder us that PTEN was deleted or lost expressed in children with NHL and the deletion or lost expression of PTEN may promote the infiltration,metastasis,progress of disease and decreased expression of PTEN may represent poor prognosis.2 The positive rate of Beclin-1 protein was significantly decreased in children with NHL and the expression of Beclin-1 protein was not related to IPI,LDH,immunophenotype or other clinicopathologic factors.This reminder us that Beclin-1 was deleted or lost expressed in children with NHL,however,it is not yet illustrative that the deleted or lost expressed was connected with prognosis.3 A significantly positive correlation was discovered between the expression of PTEN protein and Beclin-1 protein,the two kinds of tumor suppressor gene maybe cooperate in the occurrence and development of children’s NHL.4 Deficiency or lost expression of PTEN and Beclin-1 were closely related to the genesis and development of children’s NHL,combined detecting expression of the two genes probably contribute to the diagnosis and the expression of PTEN probably contribute to the prognostic judgement of children’s NHL.