International Journal of Clinical Oncology

, Volume 24, Issue 11, pp 1350–1358 | Cite as

PLEKHG5 is a novel prognostic biomarker in glioma patients

  • Mingyu Qian
  • Zihang Chen
  • Shaobo Wang
  • Xiaofan Guo
  • Zongpu Zhang
  • Wei Qiu
  • Xiao Gao
  • Jianye Xu
  • Rongrong Zhao
  • Hao XueEmail author
  • Gang LiEmail author
Original Article



PLEKHG5, a Rho-specific guanine-nucleotide exchange factor, is involved in tumor cell migration, invasion and angiogenic potential. In this study, the expression pattern, prognostic value and function of PLEKHG5 in gliomas were investigated.


Immunohistochemistry was used to determine the expression pattern of PLEKHG5 in 61 glioma patients after curative resection. Statistical analysis was performed to evaluate the diagnostic and prognostic significance of PLEKHG5. Gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and Gene set enrichment analysis (GSEA) were used to predict potential functions of PLEKHG5. Migration assay and western blot analysis determined PLEKHG5 function in glioma migration and invasion.


Increased PLEKHG5 expression levels were associated with higher glioma grades (P < 0.05). In addition, glioblastomas multiforme have higher ratio and stronger intensity of PLEKHG5 expression compared with low-grade gliomas. High expression level of PLEKHG5 indicated poorer prognosis and shorter survival time in all glioma patients (P < 0.001). GO analysis, KEGG pathway analysis and GSEA analysis suggested that PLEKHG5 was involved in glioma migration, invasion and epithelial–mesenchymal transition. Migration assay and western blot analysis revealed PLEKHG5 promoted glioma migration and invasion.


Our results demonstrated PLEKHG5 could be used as a novel prognostic biomarker and anti-tumor target for glioma patients.


Glioma PLEKHG5 Novel prognostic biomarker Tumor migration and invasion 



This work was supported by Grants from the National Natural Science Foundation of China (nos. 30872645, 81101594, 81372719, 81172403, 81402077, 81571284, 91542115, 81702468, 81874083, 81802966), National Natural Science Foundation of Shandong Province of China (no. 2017CXGC1203, 2017G006012, 2013GGE27006) and Taishan Scholars of Shandong Province of China (no. ts201511093).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Research involving human participants and/or animal

Ethical approval for using human samples in this study was obtained from the local ethics committee.

Informed consent

Patients gave consent for the use of their tumor tissues for future investigations, which had been performed for many years at time of the initial diagnosis.

Supplementary material

10147_2019_1503_MOESM1_ESM.xlsx (378 kb)
Supplementary file1 (XLSX 378 kb)


  1. 1.
    Ostrom QT, Bauchet L, Davis FG et al (2014) The epidemiology of glioma in adults: a "state of the science" review. Neurooncology 16(7):896–913Google Scholar
  2. 2.
    Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507CrossRefGoogle Scholar
  3. 3.
    Nagarajan RP, Costello JF (2009) Epigenetic mechanisms in glioblastoma multiforme. Semin Cancer Biol 19(3):188–197CrossRefGoogle Scholar
  4. 4.
    Jhaveri N, Chen TC, Hofman FM (2016) Tumor vasculature and glioma stem cells: contributions to glioma progression. Cancer Lett 380(2):545–551CrossRefGoogle Scholar
  5. 5.
    Nutt CL, Mani DR, Betensky RA et al (2003) Gene expression-based classification of malignant gliomas correlates better with survival than histological classification. Can Res 63(7):1602–1607Google Scholar
  6. 6.
    Wesseling P, Capper D (2018) WHO 2016 classification of gliomas. Neuropathol Appl Neurobiol 44(2):139–150CrossRefGoogle Scholar
  7. 7.
    Nakada M, Nakada S, Demuth T et al (2007) Molecular targets of glioma invasion. Cell Mol Life Sci CMLS 64(4):458–478CrossRefGoogle Scholar
  8. 8.
    Wang H, Han M, Whetsell W Jr et al (2014) Tax-interacting protein 1 coordinates the spatiotemporal activation of Rho GTPases and regulates the infiltrative growth of human glioblastoma. Oncogene 33(12):1558–1569CrossRefGoogle Scholar
  9. 9.
    Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420(6916):629–635CrossRefGoogle Scholar
  10. 10.
    Goicoechea SM, Awadia S, Garcia-Mata R (2014) I'm coming to GEF you: regulation of RhoGEFs during cell migration. Cell Adhes Migr 8(6):535–549CrossRefGoogle Scholar
  11. 11.
    De Toledo M, Coulon V, Schmidt S et al (2001) The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3. Oncogene 20(50):7307–7317CrossRefGoogle Scholar
  12. 12.
    Liu M, Horowitz A (2006) A PDZ-binding motif as a critical determinant of Rho guanine exchange factor function and cell phenotype. Mol Biol Cell 17(4):1880–1887CrossRefGoogle Scholar
  13. 13.
    Ngok SP, Geyer R, Liu M et al (2012) VEGF and angiopoietin-1 exert opposing effects on cell junctions by regulating the Rho GEF Syx. J Cell Biol 199(7):1103–1115CrossRefGoogle Scholar
  14. 14.
    Garnaas MK, Moodie KL, Liu ML et al (2008) Syx, a RhoA guanine exchange factor, is essential for angiogenesis in vivo. Circ Res 103(7):710–716CrossRefGoogle Scholar
  15. 15.
    Dachsel JC, Ngok SP, Lewis-Tuffin LJ et al (2013) The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and ROCK activities to promote polarized-cancer-cell migration. Mol Cell Biol 33(24):4909–4918CrossRefGoogle Scholar
  16. 16.
    Grun D, Adhikary G, Eckert RL (2019) NRP-1 interacts with GIPC1 and SYX to activate p38 MAPK signaling and cancer stem cell survival. Mol Carcinog 58(4):488–499CrossRefGoogle Scholar
  17. 17.
    Arden JD, Lavik KI, Rubinic KA et al (2015) Small-molecule agonists of mammalian diaphanous-related (mDia) formins reveal an effective glioblastoma anti-invasion strategy. Mol Biol Cell 26(21):3704–3718CrossRefGoogle Scholar
  18. 18.
    Roy R, Yang J, Moses MA (2009) Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol Off J Am Soc Clin Oncol 27(31):5287–5297CrossRefGoogle Scholar
  19. 19.
    Nakada M, Nakamura H, Ikeda E et al (1999) Expression and tissue localization of membrane-type 1, 2, and 3 matrix metalloproteinases in human astrocytic tumors. Am J Pathol 154(2):417–428CrossRefGoogle Scholar
  20. 20.
    Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2(8):563–572CrossRefGoogle Scholar
  21. 21.
    Nobes CD, Hall A (1995) Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81(1):53–62CrossRefGoogle Scholar
  22. 22.
    Sahai E, Marshall CJ (2003) Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat Cell Biol 5(8):711–719CrossRefGoogle Scholar
  23. 23.
    Tsuji T, Ishizaki T, Okamoto M et al (2002) ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts. J Cell Biol 157(5):819–830CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  1. 1.Institute of Brain and Brain-Inspired ScienceShandong UniversityJinanChina
  2. 2.Shandong Key Laboratory of Brain Function RemodelingJinanChina
  3. 3.Department of NeurosurgeryQilu Hospital of Shandong UniversityJinanChina

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