| Object To explore the most appropriate classification models in Chinese patients withdiffuse large B-cell lymphoma (DLBCL) and investigate the activation of NF-κB signalingpathway of them, meanwhile observe the impact of clinical characteristics, subgroup, andvariable biomarkers expression on prognosis.Method A total of147patients with DLBCL who were treated with CHOP-like orR-CHOP regimen were subjected to analysis. Standard two-step Envision method ofimmunohistochemical staining was used to assess the expression of CD10，BCL-6，MUM1，FOXP1，GCET1，CD5，BCL-2，Ki-67，P-p65, p52, P-IκBα. We compare thedifference of prognosis according to Hans algorithm, Choi algorithm and the activation ofNF-κB signaling pathway.Result①We assessed the clinical data of147cases of DLBCL patients by Kaplan-Meieranalysis, found that the Ann Arbor stage: Phase I-Ⅱ51cases,Ⅲ-Ⅳ96cases,3-yearoverall survival(OS) rate were87.3%and59.7%(P=0.032); IPI score0-2of92cases,3-5of55cases,3-year OS were80.6%and51.7%, respectively (P=0.001); the extranodalinvolvement≤1of112cases,≥2of35cases, the3-year OS were72.3%and46.4%(P=0.014);85cases of complete remission,62cases of less than complete remission,3-yearOS were86.95%and41.77%(P＜0.0001), there were statistically significant differences.However, regard to gender, age, LDH, B symptoms and treatment options, there was nosignificant difference (P>0.05).②For Hans model,42cases (33.1%) were classified asGCB group, while85cases as ABC group (66.9%), including7cases of the GCB by Choiadjusted to ABC,12cases of ABC adjusted to GCB. therefore, according to Choi model,47cases (37%) belonged to GCB subgroup,80cases (63%) as ABC subgroup. Choi modelsuggested GCB subtype showed much better prognosis than ABC subtype,3-year OS ofGCB and ABC group were78.5%and60.9%, respectively (P=0.047), while there was nostatistically significant difference by Hans model (P=0.285).③120cases who had theparaffin tissue were evaluated to identify the activation of NF-κB pathway. Expression of P-p65and p52were detected in30%(36/120) and35.8%(43/120) of patients,respectively; and the two protein co-expressed was16.7%(14/120) of the cases.26of36P-p65+DLBCL (72.2%) were also positive for P-IκB according to spearman rankcorrelation test P <0.0001.④The NF-κB activation were associated with adverse stage(P=0.005), high international prognostic index (P=0.010), low response rate (P=0.035), andBCL-2expression (P=0.005).⑤The3-year OS was68%for all patients. They weredivided into four groups: P-p65merely expressed group, p52merely expressed group,P-p65/p52co-expressed group and both P-p65/p52negative group, their outcomes havestatistically significant difference (3-years OS rate of51.3%,66.6%,34.6%and86.1%,respectively; P=0.01) by log-rank test. The median overall survival of P-p65/p52co-expressed group and both P-p65/p52negative group were24.3months and84.1months(P＜0.001). However, there was no significant prognosis difference between P-p65expressed group and p52expressed group (P=0.454). According to the proportion of Coxmultivariate regression model analysis the IPI (P=0.028), complete remission (P＜0.000),Ki-67≥75%(P=0.018), P-p65(P=0.032) were independent prognostic factors for OS.Conclusion Our study indicated that the Ann Arbor stage, IPI score, extranodalinvolvement and complete remission were associated with prognosis. In Chinesepopulation, compared to Hans algorithm, Choi model has an advantage to predict thedifference prognosis between subtypes that ABC group show poorer outcome. NF-κBactivation group had more adverse clinical feature. Classical pathway and alternativepathway co-activation predicted the worst survival, the median overall survival was only1year. However, there was no significant difference between classical pathway activationand alternative pathway activation. Thus, P-p65and p52expressed which are the NF-κBpathway activation symbol may be the valuable predicting factors for survival of Chinesepatients with DLBCL. |
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