Identification of differentially expressed proteins in chemotherapy-sensitive and chemotherapy-resistant diffuse large B cell lymphoma by proteomic methods.

In the present study, we employed proteomic methods to identify and quantitate differentially expressed proteins between diffuse large B cell lymphoma (DLBCL) tissues with low and high sensitivity to combinatorial cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy and explored protein networks associated with DLBCL chemoresistance to CHOP. For proteomics analysis, DLBCL tissues were collected from 14 untreated patients. Two-dimensional gel electrophoresis combined with mass spectrometry (MS) were employed to identify and quantitate differentially expressed proteins in DLBCL tissues with low or high sensitivity to CHOP chemotherapy in vitro. Nineteen proteins showing an over twofold change in the MS/MS ions score between the low sensitivity and the high sensitivity groups were identified as differentially expressed proteins and confirmed by Western blot analyses. Immunohistochemical analyses were performed in DLBCL tissue samples from 98 patients who had received four cycles of CHOP chemotherapy, which showed that expressions of the identified CHOP sensitivity biomarkers were significantly associated with therapeutic outcomes of DLBCL, suggesting that the biomarkers could be used to predict DLBCL patient outcomes. This study provides important insights into understanding the molecular basis for development of multi-drug chemoresistance in DLBCL, which may serve as a basis for identification of novel therapeutic targets and biomarkers involved in the emergence and maintenance of DLBCL resistance to CHOP.