CONCLUSION


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Our meta-analysis suggested that EGFR may serve as a useful biomarker for poor prognosis in glioma patients. In the future, targeted therapy aiming at EGFR signaling pathways may help slow the disease progression of glioma and prolong OS. To verify this result, studies with large sample sizes, covering extensive areas, with more reasonable experimental designs, more standardized diagnostic criteria, and standardized postoperative treatment are required.

Acknowledgments

This study was supported by the Key Research and Development Item from the Department of Science and Technology of Sichuan Province, China (No 2017SZ0006). Junhong Li and Ruofei Liang are the co-first authors.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Hobbs J, Nikiforova MN, Fardo DW, et al. Paradoxical relationship between the degree of EGFR amplification and outcome in glioblastomas. Am J Surg Pathol. 2012;36(8):1186–1193.

2. Pan J, Kong L, Lin S, Chen G, Chen Q, Lu JJ. The clinical significance of coexpression of cyclooxygenases-2, vascular endothelial growth factors, and epidermal growth factor receptor in nasopharyngeal carcinoma. Laryngoscope. 2008;118(11):1970–1975.

3. Matsumura T, Sugimachi K, Takahashi Y, et al. Clinical significance of GAB2, a scaffolding/docking protein acting downstream of EGFR in human colorectal cancer. Ann Surg Oncol. 2014;21(Suppl 4):S743–S749.

4. Deng W, Gu L, Li X, et al. CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells. J Transl Med. 2016;14:32.

5. Laurie SA, Goss GD. Role of epidermal growth factor receptor inhibitors in epidermal growth factor receptor wild-type non-small-cell lung cancer. J Clin Oncol. 2013;31(8):1061–1069.

6. Qin CF, Hao K, Tian XD, Xie XH, Yang YM. Combined effects of EGFR and Hedgehog signaling pathway inhibition on the proliferation and apoptosis of pancreatic cancer cells. Oncol Rep. 2012;28(2):519–526.

7. Brandes AA, Franceschi E, Tosoni A, Hegi ME, Stupp R. Epidermal growth factor receptor inhibitors in neuro-oncology: hopes and disappointments. Clin Cancer Res. 2008;14(4):957–960.

8. Ghiaseddin A, Peters KB. Use of bevacizumab in recurrent glioblastoma. CNS Oncol. 2015;4(3):157–169.

9. Krishnan S, Rao RD, James CD, Sarkaria JN. Combination of epidermal growth factor receptor targeted therapy with radiation therapy for malignant gliomas. Front Biosci. 2003;8:e1–e13.

10. Horbinski C, Hobbs J, Cieply K, Dacic S, Hamilton RL. EGFR expression stratifies oligodendroglioma behavior. Am J Pathol. 2011;179(4):1638–1644.

11. Quaranta M, Divella R, Daniele A, et al. Epidermal growth factor receptor serum levels and prognostic value in malignant gliomas. Tumori. 2007;93(3):275–280.

12. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815–2834.

13. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.

14. Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127(9):820–826.

15. Srividya MR, Thota B, Arivazhagan A, et al. Age-dependent prognostic effects of EGFR/p53 alterations in glioblastoma: study on a prospective cohort of 140 uniformly treated adult patients. J Clin Pathol. 2010;63(8):687–691.

16. Viana-Pereira M, Lopes JM, Little S, et al. Analysis of EGFR overexpression, EGFR gene amplification and the EGFRvIII mutation in Portuguese high-grade gliomas. Anticancer Res. 2008;28(2a):913–920.

17. Umesh S, Tandon A, Santosh V, et al. Clinical and immunohistochemical prognostic factors in adult glioblastoma patients. Clin Neuropathol. 2009;28(5):362–372.

18. Choi Y, Song YJ, Lee HS, et al. Epidermal growth factor receptor is related to poor survival in glioblastomas: single-institution experience. Yonsei Med J. 2013;54(1):101–107.

19. Nabika S, Kiya K, Satoh H, et al. Prognostic significance of expression patterns of EGFR family, p21 and p27 in high-grade astrocytoma. Hiroshima J Med Sci. 2010;59(4):65–70.

20. Korshunov A, Golanov A, Sycheva R, Pronin I. Prognostic value of tumour associated antigen immunoreactivity and apoptosis in cerebral glioblastomas: an analysis of 168 cases. J Clin Pathol. 1999;52(8):574–580.

21. Senetta R, Miracco C, Lanzafame S, et al. Epidermal growth factor receptor and caveolin-1 coexpression identifies adult supratentorial ependymomas with rapid unfavorable outcomes. Neuro Oncol. 2011;13(2):176–183.

22. Tini P, Cerase A, Cevenini G, Carbone SF, Miracco C, Pirtoli L. Epidermal growth factor receptor expression may correlate with survival through clinical and radiological features of aggressiveness in glioblastoma treated with radiochemotherapy. Anticancer Res. 2015;35(7):4117–4124.

23. Varela M, Ranuncolo SM, Morandi A, et al. EGF-R and PDGF-R, but not bcl-2, overexpression predict overall survival in patients with low-grade astrocytomas. J Surg Oncol. 2004;86(1):34–40.

24. Simmons ML, Lamborn KR, Takahashi M, et al. Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients. Cancer Res. 2001;61(3):1122–1128.

25. Saha R, Chatterjee U, Mandal S, Saha K, Chatterjee S, Ghosh S. Expression of phosphatase and tensin homolog, epidermal growth factor receptor, and Ki-67 in astrocytoma: a prospective study in a tertiary care hospital. Indian J Med Paediatr Oncol. 2014;35(2):149–155.

26. Abdullah KG, Ramayya A, Thawani JP, et al. Factors associated with increased survival after surgical resection of glioblastoma in octogenarians. PLoS One. 2015;10(5):e0127202.

27. Andersson U, Guo D, Malmer B, et al. Epidermal growth factor receptor family (EGFR, ErbB2–4) in gliomas and meningiomas. Acta Neuropathol. 2004;108(2):135–142.

28. Etienne MC, Formento JL, Lebrun-Frenay C, et al. Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome. Clin Cancer Res. 1998;4(10):2383–2390.

29. Michaelsen SR, Christensen IJ, Grunnet K, et al. Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution. BMC Cancer. 2013;13:402.

30. Mendrzyk F, Korshunov A, Benner A, et al. Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res. 2006;12(7 pt 1):2070–2079.

31. Chakravarti A, Seiferheld W, Tu X, et al. Immunohistochemically determined total epidermal growth factor receptor levels not of prognostic value in newly diagnosed glioblastoma multiforme: report from the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 2005;62(2):318–327.

32. Meert AP, Martin B, Delmotte P, et al. The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis. Eur Respir J. 2002;20(4):975–981.

33. Ma X, Huang J, Wu X, et al. Epidermal growth factor receptor could play a prognostic role to predict the outcome of nasopharyngeal carcinoma: a meta-analysis. Cancer Biomark. 2014;14(4):267–277.

34. Luo G, Long J, Qiu L, Liu C, Xu J, Yu X. Role of epidermal growth factor receptor expression on patient survival in pancreatic cancer: a meta-analysis. Pancreatology. 2011;11(6):595–600.

35. Guo YM, Yu WW, Zhu M, Guo CY. Clinicopathological and prognostic significance of epidermal growth factor receptor overexpression in patients with esophageal adenocarcinoma: a meta-analysis. Dis Esophagus. 2015;28(8):750–756.

36. Hong L, Han Y, Yang J, et al. Prognostic value of epidermal growth factor receptor in patients with gastric cancer: a meta-analysis. Gene. 2013;529(1):69–72.

37. Reis-Filho JS, Faoro LN, Carrilho C, Bleggi-Torres LF, Schmitt FC. Evaluation of cell proliferation, epidermal growth factor receptor, and bcl-2 immunoexpression as prognostic factors for patients with World Health Organization grade 2 oligodendroglioma. Cancer. 2000;88(4):862–869.

38. Bouvier-Labit C, Chinot O, Ochi C, Gambarelli D, Dufour H, Figarella-Branger D. Prognostic significance of Ki67, p53 and epidermal growth factor receptor immunostaining in human glioblastomas. Neuropathol Appl Neurobiol. 1998;24(5):381–388.

39. Smith JS, Tachibana I, Passe SM, et al. PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst. 2001;93(16):1246–1256.

40. Dorward NL, Hawkins RA, Whittle IR. Epidermal growth factor receptor activity and clinical outcome in glioblastoma and meningioma. Br J Neurosurg. 1993;7(2):197–199.

41. Jiang H, Ren X, Zhang W, et al. A new prognostic scoring scale for patients with primary WHO grade III gliomas based on molecular predictors. J Neurooncol. 2013;111(3):367–375.

42. Jaros E, Perry RH, Adam L, et al. Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours. Br J Cancer. 1992;66(2):373–385.

43. Zhu A, Shaeffer J, Leslie S, Kolm P, El-Mahdi AM. Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation. Int J Radiat Oncol Biol Phys. 1996;34(4):809–815.

44. Saito T, Hama S, Kajiwara Y, et al. Prognosis of cerebellar glioblastomas: correlation between prognosis and immunoreactivity for epidermal growth factor receptor compared with supratentorial glioblastomas. Anticancer Res. 2006;26(2b):1351–1357.

45. Tini P, Belmonte G, Toscano M, et al. Combined epidermal growth factor receptor and beclin1 autophagic protein expression analysis identifies different clinical presentations, responses to chemo- and radiotherapy, and prognosis in glioblastoma. Biomed Res Int. 2015;2015:208076.

46. Korshunov A, Golanov A, Sycheva R. Immunohistochemical markers for prognosis of cerebral glioblastomas. J Neurooncol. 2002;58(3):217–236.

47. Hurtt MR, Moossy J, Donovan-Peluso M, Locker J. Amplification of epidermal growth factor receptor gene in gliomas: histopathology and prognosis. J Neuropathol Exp Neurol. 1992;51(1):84–90.

48. Zhao LL, Xu KL, Wang SW, Hu BL, Chen LR. Pathological significance of epidermal growth factor receptor expression and amplification in human gliomas. Histopathology. 2012;61(4):726–736.

49. Dehais C, Laigle-Donadey F, Marie Y, et al. Prognostic stratification of patients with anaplastic gliomas according to genetic profile. Cancer. 2006;107(8):1891–1897.