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. 2021 Nov 23:13:8755-8765.
doi: 10.2147/CMAR.S336213. eCollection 2021.

Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas

Zixi Yang  1 , Feng Ling  1 , Sibei Ruan  1 , Jiajia Hu  2 , Mingxi Tang  1 , Xingwang Sun  1 , Wenbo Long  1
Affiliations

Clinical and Prognostic Implications of 1p/19q, IDH, BRAF, MGMT Promoter, and TERT Promoter Alterations, and Expression of Ki-67 and p53 in Human Gliomas

Zixi Yang et al. Cancer Manag Res. .

Abstract

Background and objective: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood.

Methods: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II-IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry.

Results: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis.

Conclusion: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.

Keywords: biomarker; correlation analysis; genetic alteration; human glioma; survival rate.

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Conflict of interest statement

The authors declare that they have no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Prognostic values of patient age, histological grade, MGMT promoter methylation, IDH mutation, TERT promoter mutation, 1p/19q codeletion, and Ki-67 and p53 expressions by Kaplan–Meier Estimates of Overall Survival in 103 gliomas.
Figure 2
Figure 2
Kaplan–Meier estimates of overall survival in the glioma molecular groups.
See this image and copyright information in PMC

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References

    1. Labreche K, Kinnersley B, Berzero G, et al. Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci. Acta Neuropathol. 2018;135(5):743–755. - PMC - PubMed
    1. Pienkowski T, Kowalczyk T, Kretowski A, Ciborowski M. A review of gliomas-related proteins. Characteristics of potential biomarkers. Am J Cancer Res. 2021;11(7):3425–3444. - PMC - PubMed
    1. van den Bent MJ. Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician’s perspective. Acta Neuropathol. 2010;120(3):297–304. - PMC - PubMed
    1. Chen WJ, He DS, Tang RX, Ren FH, Chen G. Ki-67 is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis. Asian Pac J Cancer Prev. 2015;16(2):411–420. - PubMed
    1. Jin Y, Xiao W, Song T, Feng G, Dai Z. Expression and prognostic significance of p53 in glioma patients: a meta-analysis. Neurochem Res. 2016;41(7):1723–1731. - PubMed