Article ; Online: Activation of the STAT3 signaling pathway is associated with poor survival in diffuse large B-cell lymphoma treated with R-CHOP.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2013 Volume 31, Issue 36, Page(s) 4520–4528
Abstract: ... treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). Cell line ... correlated with poor survival in patients with DLBCL treated with R-CHOP, especially those with tumors ...
| Abstract | Purpose: We previously reported that constitutive STAT3 activation is a prominent feature of the activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL). In this study, we investigated whether STAT3 activation can risk stratify patients with DLBCL. Patients and methods: By an immunohistochemical method, we investigated phosphotyrosine STAT3 (PY-STAT3) expression from 185 patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). Cell line-based siRNA experiments were also performed to generate an 11-gene, PY-STAT3 activation signature, which was used to study a previously published cohort of 222 patients with DLBCL. The STAT3 activation status determined by these two methods and by STAT3 mRNA levels were then correlated with survival. Results: PY-STAT3 was detected in 37% of DLBCL and enriched in ABC-DLBCL cases (P = .03). PY-STAT3 positivity significantly correlated with poor overall survival (OS; P = .01) and event-free survival (EFS; P = .006). Similar observations were made for high levels of STAT3 mRNA. In multivariable analysis, PY-STAT3 status (P = .02), International Prognostic Index (P = .02), and BCL2 expression (P = .046) were independent prognosticators of OS in this cohort. Among the cell-of-origin subgroups, PY-STAT3 was associated with poor EFS among non-germinal center B-cell DLBCL cases only (P = .027). Similarly, the 11-gene STAT3 activation signature correlated with poor survival in the entire DLBCL cohort (OS, P < .001; EFS, P < .001) as well as the ABC-DLBCL subgroup (OS, P = .029; EFS, P = .025). Conclusion: STAT3 activation correlated with poor survival in patients with DLBCL treated with R-CHOP, especially those with tumors of the ABC-DLBCL subtype. |
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| MeSH term(s) | Adult ; Aged ; Analysis of Variance ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antigens, CD20/metabolism ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/administration & dosage ; Disease-Free Survival ; Doxorubicin/administration & dosage ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Lymphoma, Large B-Cell, Diffuse/metabolism ; Lymphoma, Large B-Cell, Diffuse/mortality ; Male ; Middle Aged ; Predictive Value of Tests ; Prednisone/administration & dosage ; Prognosis ; Proportional Hazards Models ; RNA, Messenger/metabolism ; Retrospective Studies ; Rituximab ; STAT3 Transcription Factor/drug effects ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction/drug effects ; Tissue Array Analysis ; Treatment Outcome ; Vincristine/administration & dosage |
| Chemical Substances | Antibodies, Monoclonal, Murine-Derived ; Antigens, CD20 ; RNA, Messenger ; STAT3 Transcription Factor ; STAT3 protein, human ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) ; Prednisone (VB0R961HZT) |
| Language | English |
| Publishing date | 2013-11-12 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 604914-x |
| ISSN | 1527-7755 ; 0732-183X |
| ISSN (online) | 1527-7755 |
| ISSN | 0732-183X |
| DOI | 10.1200/JCO.2012.45.6004 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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