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Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis

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Abstract

Golgi phosphoprotein-3 (GOLPH3), an important protein in mammalian target of rapamycin (mTOR) signaling, is overexpressed in and correlates with the pathological grade of glioma. However, the potential correlation between GOLPH3 and clinical outcome in patients with glioblastoma multiforme (GBM) remains unknown. In this study, we examined GOLPH3 expression in GBM by tissue microarray and correlated this measure to patient outcome. GOLPH3 expression in tumor tissue from 97 primary GBM patients was examined by tissue microarray and immunohistochemistry. Potential effects of GOLPH3 on tumor growth were also examined in representative cell lines (U251 and U87) by downregulating GOLPH3 with RNA interference. For this cohort, the median overall survival (OS) was 12 months [95 % confidence interval (CI): 10.31–13.69 months], and the median progression-free survival (PFS) was 10 months (95 % CI: 7.33–12.67 months). Tissue microarray analysis revealed high GOLPH3 expression in 40 patients (40/97, 41.2 %) and low GOLPH3 expression in the remaining 57 patients (57/97, 58.8 %). Log-rank test showed that patients with low GOLPH3 expression had significantly longer median OS (15 versus 10 months in patients with high GOLPH3 expression, p = 0.009) and median PFS (12 versus 7 months, p = 0.015). Univariate and Cox analysis indicated that GOLPH3 was an independent prognostic factor for OS and PFS. In in vitro experiments, GOLPH3 downregulation by small interfering RNA (siRNA) suppressed proliferation and clonogenic growth in cultured cell lines. These findings demonstrate that high GOLPH3 expression is associated with poor outcome of GBM patients.

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Acknowledgments

This work was supported by the National “863” Advanced Technology Project (no. 2007AA02Z483), National Natural Science Foundation of China (no. 30973076), Program for Academic Leaders in Health Sciences in Shanghai (no. XBR2011030), and “Shu Guang” Project (no. 11SG37) in Shanghai.

Conflict of interest

The authors reported no conflicts of interest with the publication of the manuscript.

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Authors and Affiliations

  1. Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Rd, Shanghai, 200003, China

    Jinxu Zhou, Tao Xu, Rong Qin, Yong Yan, Chao Chen, Yicheng Lu, Xuehua Ding & Juxiang Chen

  2. Department of Neurosurgery, The 101st Hospital of PLA, 101 North Xingyuan Rd, Wuxi, 214000, Jiangsu, China

    Jinxu Zhou, Yuhai Wang & Xuejian Cai

  3. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, China

    Yuanyuan Chen

  4. Department of Pathology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Hongyu Yu & Chunyan Xia

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  1. Jinxu Zhou
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  2. Tao Xu
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  3. Rong Qin
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Correspondence to Juxiang Chen.

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Jinxu Zhou and Tao Xu contributed equally to the work.

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Zhou, J., Xu, T., Qin, R. et al. Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis. J Neurooncol 110, 195–203 (2012). https://doi.org/10.1007/s11060-012-0970-9

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  • DOI: https://doi.org/10.1007/s11060-012-0970-9

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