Top

International Journal of Clinical Oncology

Published in:

01-11-2019 | Glioblastoma | Original Article

PLEKHG5 is a novel prognostic biomarker in glioma patients

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

Published in: International Journal of Clinical Oncology | Issue 11/2019

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.

Available only for authorised users

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

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

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

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

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

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

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

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):1558–1569CrossRef

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

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):535–549CrossRef

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):7307–7317CrossRef

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):1880–1887CrossRef

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):1103–1115CrossRef

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):710–716CrossRef

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):4909–4918CrossRef

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):488–499CrossRef

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):3704–3718CrossRef

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):5287–5297CrossRef

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):417–428CrossRef

20.

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

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):53–62CrossRef

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):711–719CrossRef

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):819–830CrossRef

Title: PLEKHG5 is a novel prognostic biomarker in glioma patients
Authors: Mingyu Qian
Zihang Chen
Shaobo Wang
Xiaofan Guo
Zongpu Zhang
Wei Qiu
Xiao Gao
Jianye Xu
Rongrong Zhao
Hao Xue
Gang Li
Publication date: 01-11-2019
Publisher: Springer Singapore
Keywords: Glioblastoma
Glioma
Glioma
Glioblastoma
Glioblastoma
Glioma
Biomarkers
Published in: International Journal of Clinical Oncology / Issue 11/2019
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-019-01503-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 11/2019

The impact of programmed cell death-ligand 1 (PD-L1) and CD8 expression in grade 3 endometrial carcinomas

Clinical results of carbon-ion radiotherapy with separation surgery for primary spine/paraspinal sarcomas

Clinical features and treatment outcome of desmoid-type fibromatosis: based on a bone and soft tissue tumor registry in Japan

Efficacy of chemotherapy for older patients with gastric cancer: a multicenter retrospective cohort study

Efficacy of daikenchuto, a traditional Japanese Kampo medicine, for postoperative intestinal dysfunction in patients with gastrointestinal cancers: meta-analysis

CDC20 and its downstream genes: potential prognosis factors of osteosarcoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer