Clinical Significance And Prognostic Value Of Fbxw7 Protein In Diffuse Large B-cell Lymphoma

Background and ObjectiveDiffuse Large B Cell Lymphoma(DLBCL)is the most common type of non-Hodgkin’s lymphoma(NHL),accounting for 30%to 40%of adult NHL i n Western countries.The incidence rate in China is about 50.7%.With the us e of rituximab,the prognosis of patients with DLBCL has improved significan tly,but 30%to 40%of patients still have refractory or relapse.Studies have shown that its prognosis is closely related to its biological characteristics,such as high expression of c-Myc,Bcl-2,Bcl-6,and P53 mutation.Fbxw7(F-box and WD repeat domain-containing 7)is a specific recognition substrate for th e Skp1-CUL1-F-box(SCF)ubiquitin ligase E3 complex.The key factor,whic h can target the degradation of c-Myc,CyclinE,c-Jun and Notch,is a broad tumor suppressor gene.Deletion of Fbxw7 expression has been found in many human malignancies.Based on the lack of research on Fbxw7 and DLBCL,t his study aims to analyze the clinical significance and prognostic value of Fb xw7 protein in DLBCL by analyzing the expression of Fbxw7 protein in DLB CL and the correlation between Fbxw7 protein and c-Myc protein expression.Furthermore,it will provide new targets for the diagnosis and treatment of pat ients with DLBCL in the future.PurposeTo observe the expression of Fbxw7 and c-Myc proteins in newly diagno sed diffuse large B-cell lymphoma,and to explore the correlation between Fbx w7 protein and c-Myc protein in diffuse large B-cell lymphoma,and The relat ionship between the expression of Fbxw7 protein and the general clinical feat ures,efficacy and prognosis of patients with DLBCL.MethodsParaffin-embedded specimens and clinical data of 72 patients with newly diagnosed DLBCL who had undergone immunohistochemical examination of c-Myc protein were collected,and 22 specimens of lymph node reactive hyperpl asia were selected as control group.Immunohistochemistry was used to detect the expression of Fbxw7 protein in DLBCL tissues and lymph node reactive hyperplasia tissues.The score of≥1 of Fbxw7 immunohistochemical staining was defined as positive group,and<1 point was defined as negative group.T he clinical characteristics and prognosis of the two groups were analyzed.The relevant data were analyzed by SPSS21.0 statistical software.The independen t sample data of the classification were tested byχ~2;the prognostic single fac tor analysis was performed by Kaplan-Meier method,and the multivariate anal ysis was analyzed by COX regression model.Results1.Of the 72 DLBCL tissues,46 were positive for Fbxw7 protein(63.89%),26were negative for Fbxw7 protein(36.11%);19 of 22 lymph node reactive hyperplasia were positive(86.36%),and 3 were negative(16.64%),the difference was statistically significant(χ~2=3.990 P=0.046<0.05).2.There were no significant differences in Fbxw7 protein expression between the age,sex,stage,IPI score,B symptom,ECOG score,LDH,andβ2microglobulin grouping(P>0.05).3.Among the 46 patients with positive Fbxw7 protein,30 patients(65.22%)reached CR after initial treatment,16 patients(34.78%)did not reach CR,and 14patients(53.85%)reached CR in 26 patients with negative Fbxw7 protein.CR was not reached in 12 cases(46.15%).There was no significant difference in CR between Fbxw7 positive group and negative group after initial treatment(P=0.342).4.Among 72 cases of DLBCL,22 cases were positive for c-Myc protein,10cases were positive for Fbxw7 protein(45.45%),12 cases were negative for Fbxw7protein(54.54%),36 cases were positive for Fbxw7 protein(72.0%)out of 50 cases negative for c-Myc protein.Fbxw7 protein was negative in 14 cases(28.00%),the difference was statistically significant(r=0.255,P=0.031<0.05).There was a negative correlation between Fbxw7 and c-Myc protein.5.Among the 72 cases of DLBCL,45 cases were in the GCB group,of which 33cases were positive for Fbxw7 protein(73.33%),12 cases were negative for protein(26.67%),and of the 27 cases of non-GCB group,13 cases were positive for Fbxw7protein(48.15%).14 cases of Fbxw7 protein negative(51.85%),the difference was statistically significant(χ~2=4.639,P=0.031<0.05).The 3-year OS in the GCB group was 89.9%,and the 3-year OS in the non-GCB group was 73.9%.The difference was statistically significant(χ~2=4.823 P=0.028<0.05).6.72 patients with DLBCL were followed up by telephone.The initial treatment was used as the starting point.The death,loss of follow-up or deadline(December 31,2018)was used as the end point.A total of 70 complete follow-up data were obtained.The follow-up rate was 97.2.%.70 complete cases were included in the survival analysis.The 3-year OS and PFS of the Fbxw7-positive group were 88.3%and 82.0%,respectively,and the 3-year OS and PFS of the Fbxw7-negative group were 70.2%and 60.1%,respectively.There were significant differences in OS and PFS between the two groups(P=0.038,0.034).It is indicated that down-regulation of Fbxw7 protein expression is a poor prognostic factor affecting OS and PFS in patients with newly diagnosed DLBCL.COX regression analysis was performed on factors such as Fbxw7 expression.Down-regulation of Fbxw7 expression was an independent risk factor for OS and PFS(P=0.041,0.033).Conclusion1.Fbxw7 protein is down-regulated in DLBCL compared with non-tumor tissue,andis more pronounced in non-GCB-type DLBCL than in GCB-type;2.There was a negative correlation between Fbxw7 and c-Myc protein expression;3.Down-regulation of Fbxw7 expression is an independent risk factor for OS and PFS in patients with newly diagnosed DLBCL.