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Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma.

Publication ,  Journal Article
Ok, CY; Chen, J; Xu-Monette, ZY; Tzankov, A; Manyam, GC; Li, L; Visco, C; Montes-Moreno, S; Dybkær, K; Chiu, A; Orazi, A; Zu, Y; Bhagat, G ...
Published in: Clinical cancer research : an official journal of the American Association for Cancer Research
October 2014

Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of phosphorylated STAT3 (pSTAT3) on prognosis are limited.We evaluated expression of pSTAT3 in de novo DLBCL using immunohistochemistry, gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results were analyzed in correlation with cell-of-origin (COO), critical lymphoma biomarkers, and genetic translocations.pSTAT3 expression was observed in 16% of DLBCL and was associated with advanced stage, multiple extranodal sites of involvement, activated B-cell-like (ABC) subtype, MYC expression, and MYC/BCL2 expression. Expression of pSTAT3 predicted inferior overall survival (OS) and progression-free survival (PFS) in patients with de novo DLBCL. When DLBCL cases were stratified according to COO or MYC expression, pSTAT3 expression did not predict inferior outcome, respectively. Multivariate analysis showed that the prognostic predictability of pSTAT3 expression was due to its association with the ABC subtype, MYC expression, and adverse clinical features. GEP demonstrated upregulation of genes, which can potentiate function of STAT3. GSEA showed the JAK-STAT pathway to be enriched in pSTAT3(+) DLBCL.The results of this study provide a rationale for the ongoing successful clinical trials targeting the JAK-STAT pathway in DLBCL.

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Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

October 2014

Volume

20

Issue

19

Start / End Page

5113 / 5123

Related Subject Headings

  • Vincristine
  • Tumor Suppressor Protein p53
  • Tumor Burden
  • Signal Transduction
  • STAT3 Transcription Factor
  • Rituximab
  • Proto-Oncogene Proteins c-akt
  • Prognosis
  • Prednisone
  • Phosphorylation
 

Citation

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Ok, C. Y., Chen, J., Xu-Monette, Z. Y., Tzankov, A., Manyam, G. C., Li, L., … Young, K. H. (2014). Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 20(19), 5113–5123. https://doi.org/10.1158/1078-0432.ccr-14-0683
Ok, Chi Young, Jiayu Chen, Zijun Y. Xu-Monette, Alexandar Tzankov, Ganiraju C. Manyam, Ling Li, Carlo Visco, et al. “Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research 20, no. 19 (October 2014): 5113–23. https://doi.org/10.1158/1078-0432.ccr-14-0683.
Ok CY, Chen J, Xu-Monette ZY, Tzankov A, Manyam GC, Li L, et al. Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2014 Oct;20(19):5113–23.
Ok, Chi Young, et al. “Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 20, no. 19, Oct. 2014, pp. 5113–23. Epmc, doi:10.1158/1078-0432.ccr-14-0683.
Ok CY, Chen J, Xu-Monette ZY, Tzankov A, Manyam GC, Li L, Visco C, Montes-Moreno S, Dybkær K, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Choi WWL, van Krieken JH, Huh J, Zhao X, Ponzoni M, Ferreri AJM, Bertoni F, Farnen JP, Møller MB, Piris MA, Winter JN, Medeiros LJ, Young KH. Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2014 Oct;20(19):5113–5123.

Published In

Clinical cancer research : an official journal of the American Association for Cancer Research

DOI

EISSN

1557-3265

ISSN

1078-0432

Publication Date

October 2014

Volume

20

Issue

19

Start / End Page

5113 / 5123

Related Subject Headings

  • Vincristine
  • Tumor Suppressor Protein p53
  • Tumor Burden
  • Signal Transduction
  • STAT3 Transcription Factor
  • Rituximab
  • Proto-Oncogene Proteins c-akt
  • Prognosis
  • Prednisone
  • Phosphorylation