STAT3 expression is associated with poor survival in non-elderly adult patients with newly diagnosed multiple myeloma

Sung-Hoon Jung; Seo-Yeon Ahn; Hyun-Woo Choi; Myung-Geun Shin; Seung-Shin Lee; Deok-Hwan Yang; Jae-Sook Ahn; Yeo-Kyeoung Kim; Hyeoung-Joon Kim; Je-Jung Lee

doi:10.5045/br.2017.52.4.293

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Original Article

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Blood Res 2017; 52(4):

Published online December 31, 2017

https://doi.org/10.5045/br.2017.52.4.293

STAT3 expression is associated with poor survival in non-elderly adult patients with newly diagnosed multiple myeloma

Sung-Hoon Jung^1,#, Seo-Yeon Ahn^1,#, Hyun-Woo Choi², Myung-Geun Shin², Seung-Shin Lee¹, Deok-Hwan Yang¹, Jae-Sook Ahn¹, Yeo-Kyeoung Kim¹, Hyeoung-Joon Kim¹, and Je-Jung Lee^1*

Author Info. +

¹Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

²Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Correspondence to : Je-Jung Lee, M.D., Ph.D. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322, Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeonnam 58128, Korea. drjejung@chonnam.ac.kr

Received: May 9, 2017; Revised: June 28, 2017; Accepted: July 8, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background

Signal transducer and activator of transcription 3 (STAT3) is not only a key signaling molecule in the regulation of growth but is also involved in malignant transformation. We investigated the prognostic significance of STAT3 expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly diagnosed multiple myeloma (MM).

Methods

Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138.

Results

PY-STAT3 positivity was detected in 10 patients (10.6%), including three who showed strong expression. PY-STAT3-positive patients had higher serum C-reactive protein and calcium levels at diagnosis than did PY-STAT3-negative patients. PY-STAT3 positivity had predictive value for poor progression-free survival (PFS; P=0.001) and overall survival (OS; P=0.003). Among the 60 patients who received frontline autologous stem cell transplantation, PY-STAT3-positive patients had poorer PFS than did PY-STAT3-negative patients (4.2 vs. 19.2 mo, respectively; P=0.013). Multivariate analysis identified PY-STAT3 expression as an independent prognostic factor for PFS (relative risk [RR]=2.706, P=0.014) and OS (RR=3.091, P=0.044).

Conclusion

These data show that PY-STAT3 positivity, as determined using dual IHC, is a marker of poor prognosis in non-elderly adult patients with MM.

Keywords STAT3, Multiple myeloma, Prognosis

Article

Original Article

Blood Res 2017; 52(4): 293-299

Published online December 31, 2017 https://doi.org/10.5045/br.2017.52.4.293

STAT3 expression is associated with poor survival in non-elderly adult patients with newly diagnosed multiple myeloma

Sung-Hoon Jung^1,#, Seo-Yeon Ahn^1,#, Hyun-Woo Choi², Myung-Geun Shin², Seung-Shin Lee¹, Deok-Hwan Yang¹, Jae-Sook Ahn¹, Yeo-Kyeoung Kim¹, Hyeoung-Joon Kim¹, and Je-Jung Lee^1*

¹Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

²Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Correspondence to:Je-Jung Lee, M.D., Ph.D. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322, Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeonnam 58128, Korea. drjejung@chonnam.ac.kr

Received: May 9, 2017; Revised: June 28, 2017; Accepted: July 8, 2017

Abstract

Background

Methods

Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138.

Results

Conclusion

These data show that PY-STAT3 positivity, as determined using dual IHC, is a marker of poor prognosis in non-elderly adult patients with MM.

Keywords: STAT3, Multiple myeloma, Prognosis

Abstract

Fig 1.

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Figure 1.

Dual immunohistochemical staining of bone marrow sections obtained at diagnosis shows (A, B) plasma cells positive for CD138 (brown cell membranes) and negative for STAT3 expression and (C, D) plasma cells positive for both CD138 and STAT3 (red nuclei, ×400, ×1,000).

Blood Research 2017; 52: 293-299https://doi.org/10.5045/br.2017.52.4.293

Fig 2.

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Figure 2.

Kaplan–Meier survival curves for progression-free survival and overall survival according to (A, B) PY-STAT3-positivity and (C, D) intensity of PY-STAT3 expression.

Blood Research 2017; 52: 293-299https://doi.org/10.5045/br.2017.52.4.293

Fig 3.

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Figure 3.

Kaplan–Meier survival curves for (A) progression-free survival and (B) overall survival according to PY-STAT3 positivity in patients who underwent frontline autologous stem cell transplantation.

Blood Research 2017; 52: 293-299https://doi.org/10.5045/br.2017.52.4.293

Table 1 Baseline clinical characteristics of the 94 patients with multiple myeloma according to STAT3 expression.

^a)Standard risk: del(17) (−), del(13) (−) as determined by fluorescence in situ hybridization and a normal karyotype; high risk: del(17) (+), 1q/del1p (+), t(4;14)..

Abbreviations: ASCT, autologous stem cell transplantation; BM, bone marrow; ECOG, Eastern Cooperative Oncology Group; eGFR, estimated glomerular filtration rate; N, number; PS, performance status; PYSTAT-3, phosphotyrosine-signal transducer and activator of transcription 3..

Table 2 Univariate analysis of progression-free survival (PFS) and overall survival (OS) in 94 patients with multiple myeloma.

Abbreviations: ALC, absolute lymphocyte count; BM, bone marrow; ECOG, Eastern Cooperative Oncology Group; eGFR, estimated glomerular filtration rate; ISS, International Staging System; LDH, lactate dehydrogenase; PS, performance status; STAT3, signal transducer and activator of transcription 3; ULN, upper limit of normal value..

Table 3 Multivariate analysis of progression-free survival (PFS) and overall survival (OS) in 94 patients with multiple myeloma.

Abbreviations: CI, confidence interval; eGFR, estimated glomerular filtration rate; ISS, International Staging System; LDH, lactate dehydrogenase; STAT3, signal transducer and activator of transcription 3; ULN, upper limit of normal value..