Objective:1) To study distributions of germinal centerB-cell like(GCB) subgroup and non-GCB subgroup in Uygur patients with Diffuse large B cell lymphoma (DLBCL);2) To investigate expression and significance of apoptosis related proteins and multidrug resistance-related protein1(MRP1) gene in GCB subgroup and non-GCB subgroup in Uygur patients with DLBCL;3) To investigate expression and significance of PI3K/Akt/mTOR pathway related proteins in Uygur patients with DLBCL. Methods:1) Standard two-step Envision method of Immunohistochemistry(IHC)was used to assess the expression of CD10, bcl-6, MUM1, GCET1and FOXP1. according to Choi algorithm, sixty Uygur DLBCL were classified into the GCB subgroup or the non-GCB subgroup;2) Apopotosis precent of samples were examined by cell flow cytometry;3) The expression of Bcl-2, Bcl-xL, Bax, survivin were examined by Western blot;4) The level of mRNA expression of resistant drug gene MRP1were examined by RT-PCR;5) The expression of Phosphorylated PI3K, Akt and mTOR were examined by Western blot;6) The clinicopathologic features and follow-up data were analyzed by the Kaplan-Meier method, Log-rank test and Χ2test. Results:1) In60cases of Uygur DLBCL,18cases(30%)were GCB subtypes and42cases (70%) were non-GCB subtypes, moreover, non-GCB subtype showed poor prognosis than that of GCB (42.1%vs74.5%, P<0.05). Ann Arbor stage, IPI and immunophenotype are independent prognostic factors for in Uygur patients with DLBCL in Xinjiang (P<0.05);2) The apoptosis rate of GCB group and non-GCB group were43.08±9.72%,56.17±6.88%respectively, the different between above groups was statistically significant (P<0.05);3) Bcl-2expression in non-GCB subgroup (50%) was significantly higher than that in GCB subgroup (16.7%) (P<0.05). Survivin expression in non-GCB subgroup (66.7%) was significantly higher than that in GCB subgroup (27.8%)(P<0.01). Expression of Bax and bcl-xL were no significant differences in GCB and non-GCB subgroups (P>0.05);4) Bcl-2and survivin may be potential prognostic markers for Uygur patients with DLBCL in Xinjiang (P<0.05), but the expression of Bax and bcl-xL had no impact on the OS (P>0.05);5) MRP1mRNA expression in non-GCB (66.7%) was significantly higher than that in GCB (33.3%)(P<0.05). Groups of MRP1negtive expression showed much better prognosis than groups of MRP1positive expression according to survival analysis (72.9%vs30.4%, P=0.006);6) Expression of AKt and mTOR were significant differences in GCB and non-GCB subgroups (P<0.05) but expression of PI3K were no significant differences in GCB and non-GCB subgroups (P>0.05);7) There were significant correlation between expression of AKt and age (P<0.05), but were not related to the sex, stage, B symptoms, level of LDH, extranodal number and IPI in Uygur patients with DLBCL in Xinjiang;8) There were significant correlation between expression of AKt and bcl-2(P<0.05) but expression of p-PI3K and p-mTOR were not related to expression of bcl-2(P>0.05). Expression of AKt and mTOR were closely related to expression of survivin (P<0.05), but there were no significant correlation between expression of p-PI3K and survivin (P>0.05);9) Expression of p-AKt and p-mTOR were closely related to expression of MRP1mRNA (P<0.05), but there were no significant correlation between expression of PI3K and MRP1mRNA (P>0.05);10) p-mTOR expression may be a potential prognostic marker for Uygur patients with DLBCL in Xinjiang (P<0.05), but the expression of p-PI3K and p-AKt had no impact on survival of Uygur patients with DLBCL (P>0.05). Conclusions:1) According to the Choi algorithm, majority of Uygur DLBCL were belong to non-GCB group, moreover, non-GCB subgroup showed more poor prognosis than that of GCB subgroup. Ann Arbor stage, IPI and Choi immunophenotype may be independent prognostic factors for Uygur DLBCL in Xinjiang;2) Apoptosis and multidrug resistance(MDR)may have different role in GCB and non-GCB subtype. Bcl-2, survivin and MRP1may be predictors of prognosis in Uygur patients with DLBCL in Xinjiang;3) PI3K/AKT/mTOR pathway may has different role in GCB and non-GCB subtype, moreover, is closely related to apoptosis and MDR inUygur DLBCL in Xinjiang. |