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PLEKHG5 is a novel prognostic biomarker in glioma patients

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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

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References

  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):896–913

    CAS  Google Scholar 

  2. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507

    Article  CAS  Google Scholar 

  3. Nagarajan RP, Costello JF (2009) Epigenetic mechanisms in glioblastoma multiforme. Semin Cancer Biol 19(3):188–197

    Article  CAS  Google Scholar 

  4. Jhaveri N, Chen TC, Hofman FM (2016) Tumor vasculature and glioma stem cells: contributions to glioma progression. Cancer Lett 380(2):545–551

    Article  CAS  Google Scholar 

  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):1602–1607

    CAS  Google Scholar 

  6. Wesseling P, Capper D (2018) WHO 2016 classification of gliomas. Neuropathol Appl Neurobiol 44(2):139–150

    Article  CAS  Google Scholar 

  7. Nakada M, Nakada S, Demuth T et al (2007) Molecular targets of glioma invasion. Cell Mol Life Sci CMLS 64(4):458–478

    Article  CAS  Google Scholar 

  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):1558–1569

    Article  CAS  Google Scholar 

  9. Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420(6916):629–635

    Article  CAS  Google Scholar 

  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):535–549

    Article  Google Scholar 

  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):7307–7317

    Article  Google Scholar 

  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):1880–1887

    Article  CAS  Google Scholar 

  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):1103–1115

    Article  CAS  Google Scholar 

  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):710–716

    Article  CAS  Google Scholar 

  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):4909–4918

    Article  CAS  Google Scholar 

  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):488–499

    Article  CAS  Google Scholar 

  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):3704–3718

    Article  CAS  Google Scholar 

  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):5287–5297

    Article  CAS  Google Scholar 

  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):417–428

    Article  CAS  Google Scholar 

  20. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2(8):563–572

    Article  CAS  Google Scholar 

  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):53–62

    Article  CAS  Google Scholar 

  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):711–719

    Article  CAS  Google Scholar 

  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):819–830

    Article  CAS  Google Scholar 

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Acknowledgements

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).

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Authors and Affiliations

  1. Institute of Brain and Brain-Inspired Science, Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, China

    Mingyu Qian, Zihang Chen, Shaobo Wang, Xiaofan Guo, Zongpu Zhang, Wei Qiu, Xiao Gao, Jianye Xu, Rongrong Zhao, Hao Xue & Gang Li

  2. Shandong Key Laboratory of Brain Function Remodeling, Jinan, Shandong, China

    Mingyu Qian, Zihang Chen, Shaobo Wang, Xiaofan Guo, Zongpu Zhang, Wei Qiu, Xiao Gao, Jianye Xu, Rongrong Zhao, Hao Xue & Gang Li

  3. Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

    Hao Xue & Gang Li

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  1. Mingyu Qian
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  2. Zihang Chen
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  3. Shaobo Wang
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  4. Xiaofan Guo
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  5. Zongpu Zhang
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  6. Wei Qiu
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  7. Xiao Gao
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  8. Jianye Xu
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  9. Rongrong Zhao
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  10. Hao Xue
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  11. Gang Li
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Corresponding authors

Correspondence to Hao Xue or Gang Li.

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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.

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Cite this article

Qian, M., Chen, Z., Wang, S. et al. PLEKHG5 is a novel prognostic biomarker in glioma patients. Int J Clin Oncol 24, 1350–1358 (2019). https://doi.org/10.1007/s10147-019-01503-0

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  • DOI: https://doi.org/10.1007/s10147-019-01503-0

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