title: Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis.
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.
authors.affiliation: Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Rd, Shanghai, 200003, China.
authors.forename: Jinxu
authors.initials: J
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Rong
authors.initials: R
authors.lastname: Qin
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Xia
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Lu
authors.forename: Xuehua
authors.initials: X
authors.lastname: Ding
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Wang
authors.forename: Xuejian
authors.initials: X
authors.lastname: Cai
authors.forename: Juxiang
authors.initials: J
authors.lastname: Chen
mesh_terms: D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering