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Activation of the STAT3 signaling pathway is associated with poor survival in diffuse large B-cell lymphoma treated with R-CHOP.

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机构： [1]Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin [2]West China Hospital, West China School of Medicine of Sichuan University, Chengdu, China [3]University of Nebraska Medical Center, Omaha, NE [4]Albert Einstein College of Medicine, Bronx, NY [5]University of Arizona, Tucson, AZ [6]University ofWu¨rzburg,Wu¨rzburg, Germany [7]Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Oslo, Norway [8]Hospital Clinic, University of Barcelona, Barcelona, Spain [9]Oregon Health and Science University, Portland, OR [10]British Columbia Cancer Agency, Vancouver, British Columbia, Canada [11]Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH [12]Center for Cancer Research, National Cancer Institute, Bethesda, MD

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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. 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. 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). 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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出版当年[2013]版：

大类 | 1 区

医学

小类 | 1 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区肿瘤学

第一作者：

第一作者机构： [1]Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin [3]University of Nebraska Medical Center, Omaha, NE

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通讯机构： [*1]Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE

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