Detection of human cytomegalovirus in glioblastoma among Taiwanese subjects.

Ching-Fen Yang,Donald Ming-Tak Ho,Chih-Yi Hsu,Hsiang-Ling Ho,Shih-Chieh Lin,Michael Nevels

doi:10.1371/journal.pone.0179366

Ching-Fen Yang, Donald Ming-Tak Ho + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0179366

Copy DOI

Abstract

The relationship between human cytomegalovirus (HCMV) and glioblastoma (GBM) has been debated for more than a decade. We investigated the presence of HCMV genes, RNA and protein in GBMs and their relationships with tumor progression. Results of quantitative PCR for HCMV UL73, nested PCR for HCMV UL144, in situ hybridization (ISH) for RNA transcript, and immunohistochemistry (IHC) for protein expression and their relationship to the prognosis of 116 patients with GBM were evaluated. Nine (7.8%) cases revealed a low concentration of HCMV UL73, and only 2 of the 9 (1.7%) cases showed consistent positivity on repeat PCR testing. HCMV UL144, ISH and IHC assays were all negative. The HCMV UL73 positive cases did not show significant difference in the clinicopathological characters including age, gender, Karnofsky performance status, extent of resection, bevacizumab treatment, isocitrate dehydrogenase 1 mutation, O6-methylguanine-DNA-methyltranferase status and Ki67 labeling index, and did not reveal prognostic significance. As only one HCMV gene was detected at low concentration in 7.8% of GBMs and there was no evidence of transcription, protein expression or prognostic impact, we cannot conclude a relationship between HCMV and GBM in Taiwanese patients.

Highlights

Glioblastoma (GBM) is the most common malignant neoplasm of the central nervous system
After primary infection of human cytomegalovirus (HCMV), the virus persists in latency and involves expression of specific latency-associated viral gene products in the latently infected cell [35]
Since Cobbs and colleagues reported the presence of HCMV in malignant gliomas [8], the relationship between HCMV and GBM has been debated for more than a decade

Summary

Introduction

Glioblastoma (GBM) is the most common malignant neoplasm of the central nervous system. In comparing with other common malignancies in Taiwan, such as colon and breast cancers, its survival is still poor. Studies to identify new therapeutic targets and/or better managements for GBM are needed. The seroprevalence of human cytomegalovirus (HCMV) is high [3] and the virus establishes a lifelong latency in the host with periodic reactivations [4].

Methods

Results

Conclusion