Expression of Fbxw7 protein in diffuse large B-cell lymphoma and its clinical significance / 白血病·淋巴瘤

ABSTRACT

Objective:To explore the expression of Fbxw7 protein and its clinical significance in diffuse large B-cell lymphoma (DLBCL), and to provide a basis for prognostic judgement and searching the new therapeutic targets of DLBCL.Methods:A total of 72 patients with newly diagnosed DLBCL who received immunohistochemical detection of c-myc protein from January 2011 to September 2017 in Cancer Hospital Affilicoted to Zhengzhou University were enrolled. The paraffin-embedded specimens after lymph node biopsy and the clinical data of patients were also collected. At the same time, 22 samples of lymph node reactive hyperplasia were selected as the control group. Immunohistochemical method was used to detect the expression of Fbxw7 protein in DLBCL tissues and control tissues. The relationship between the expression of Fbxw7 protein and c-myc protein, the association of Fbxw7 protein expression with DLBCL patients' clinicopathological characteristics, efficacy and prognosis were analyzed.Results:The positive rate of Fbxw7 protein in DLBCL tissues was lower than that in control tissues, and the difference was statistically significant [63.89% (46/72) vs. 86.36% (19/22), χ 2 = 3.990, P = 0.046]. Among DLBCL patients, the positive rate of Fbxw7 protein in non-germinal center B cell (non-GCB) group was lower than that in germinal center B cell (GCB) group, and the difference was statistically significant [48.15% (13/27) vs. 73.33% (33/45), χ 2 = 4.639, P = 0.031]. There were no statistically significant differences in the positive rate of Fbxw7 protein among patients with different age, gender, neoplasm staging, international prognostic index (IPI) scores, B symptom, Eastern Cooperative Oncology Group (ECOG) score, lactate dehydrogenase (LDH) level, β 2 microglobulin level, and therapeutic efficacy after initial treatment (all P > 0.05). In DLBCL tissues, the expression of Fbxw7 and c-myc protein was negatively correlated ( r = -0.255, P = 0.031). The 3-year overall survival (OS) rate and 3-year progression-free survival (PFS) rate (88.3% and 82.0%) of the Fbxw7 positive group were higher than those of the Fbxw7 negative group (70.2% and 60.1%). Cox multivariate analysis showed that the down-regulation of Fbxw7 protein expression was an independent risk factor affecting OS and PFS in DLBCL patients ( HR = 3.656, 95% CI 1.055-12.674, P = 0.041; HR = 2.897, 95% CI 1.092-7.688, P = 0.033). Conclusions:The expression of Fbxw7 protein and c-myc protein in DLBCL patients is negatively correlated. Fbxw7 protein is down-regulated in DLBCL, and it is more obvious in non-GCB subtype. The down-regulated expression of Fbxw7 protein is related to the poor prognosis of DLBCL, and Fbxw7 may become a new therapeutic target of DLBCL.