The prognostic value of C-X-C motif chemokine receptor 4 in patients with sporadic malignant peripheral nerve sheath tumors

Chao Zhang,Wen-Ya Zhou,Ji-Long Yang,Fang-Yuan Chang

doi:10.1186/s40880-017-0246-z

Abstract

BackgroundRecent studies indicate that C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated malignant peripheral nerve sheath tumor (MPNST) cells and promote their proliferation. In this study, we measured the expression of CXCR4, CXCL12, and Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and investigated their prognostic values.MethodsCXCR4, CXCL12, and Cyclin D1 protein expression in samples from 58 Chinese patients with sporadic MPNST was assessed with immunohistochemical staining. Their prognostic values were evaluated with Kaplan–Meier analysis and a log-rank test. Multivariate Cox regression analysis was used to identify independent prognostic factors.ResultsHigh expression of CXCR4, CXCL12, and Cyclin D1 was observed in 19 (32.8%), 32 (55.2%), and 16 (27.6%) samples, respectively. CXCR4 expression was positively correlated with CXCL12 expression (r = 0.334, P = 0.010) and Cyclin D1 expression (r = 0.309, P = 0.018). Patients with high CXCR4 expression showed longer overall survival than those with low CXCR4 expression (χ2 = 4.642, P = 0.031).ConclusionHigh CXCR4 expression may define a specific subtype of sporadic MPNST with favorable prognosis.

Highlights

Recent studies indicate that C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibroma‐ tosis 1-associated malignant peripheral nerve sheath tumor (MPNST) cells and promote their proliferation
The role of CXCR4 in sporadic MPNSTs is unclear. We addressed this question by measuring the expression of CXCR4, CXCL12, and Cyclin D1 proteins in tumor samples from Chinese patients with sporadic MPNST
In the present study, we identified a significant increase in CXCL4, CXCL12, and Cyclin D1 expression in tumor samples from Chinese patients with sporadic MPNST

Summary

Introduction

Recent studies indicate that C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibroma‐ tosis 1-associated malignant peripheral nerve sheath tumor (MPNST) cells and promote their proliferation. Compared with sporadic MPNSTs, NF1-associated MPNSTs usually develop in young adults, frequently relapse (in approximately 50% of patients), and lead to a dismal prognosis partly because of the high mutation frequency of NF1 gene [8]. Traditional treatment modalities, such as surgery, chemotherapy, and radiotherapy, have limited therapeutic effects on

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Conclusion