Human Cytomegalovirus Seropositivity and Viral DNA in Breast Tumors Are Associated with Poor Patient Prognosis

Zelei Yang; Xiaoyun Tang; Maria Eloisa Hasing; Xiaoli Pang; Sunita Ghosh; Todd P W McMullen; David N Brindley; Denise G Hemmings

doi:10.3390/cancers14051148

Human Cytomegalovirus Seropositivity and Viral DNA in Breast Tumors Are Associated with Poor Patient Prognosis

Cancers (Basel). 2022 Feb 23;14(5):1148. doi: 10.3390/cancers14051148.

Authors

Zelei Yang^{1

2}, Xiaoyun Tang^{1

2}, Maria Eloisa Hasing³, Xiaoli Pang^{3

4}, Sunita Ghosh⁵, Todd P W McMullen^{2

6}, David N Brindley^{1

2}, Denise G Hemmings^{2

7}

Affiliations

¹ Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, Canada.
² Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada.
³ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2B7, Canada.
⁴ Public Health Laboratory, Alberta Precision Laboratory, Edmonton, AB T6G 2J2, Canada.
⁵ Medical Oncology, Mathematical and Statistical Sciences, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
⁶ Department of Surgery, University of Alberta, Edmonton, AB T6G 2R7, Canada.
⁷ Medical Microbiology and Immunology, Obstetrics and Gynecology, Women and Children's Health Research Institute, Li Ka Shing Institute of Virology, Cardiovascular Research Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada.

Abstract

Human cytomegalovirus (HCMV) infects 40-70% of adults in developed countries. Detection of HCMV DNA and/or proteins in breast tumors varies considerably, ranging from 0-100%. In this study, nested PCR to detect HCMV glycoprotein B (gB) DNA in breast tumors was shown to be sensitive and specific in contrast to the detection of DNA for immediate early genes. HCMV gB DNA was detected in 18.4% of 136 breast tumors while 62.8% of 94 breast cancer patients were seropositive for HCMV. mRNA for the HCMV immediate early gene was not detected in any sample, suggesting viral latency in breast tumors. HCMV seropositivity was positively correlated with age, body mass index and menopause. Patients who were HCMV seropositive or had HCMV DNA in their tumors were 5.61 (CI 1.77-15.67, p = 0.003) or 5.27 (CI 1.09-28.75, p = 0.039) times more likely to develop Stage IV metastatic tumors, respectively. Patients with HCMV DNA in tumors experienced reduced relapse-free survival (p = 0.042). Being both seropositive with HCMV DNA-positive tumors was associated with vascular involvement and metastasis. We conclude that determining the seropositivity for HCMV and detection of HCMV gB DNA in the breast tumors could identify breast cancer patients more likely to develop metastatic cancer and warrant special treatment.

Keywords: PCR methods; glycoprotein B; latency; metastasis; oncomodulatory; relapse-free survival; tumor recurrence.

Abstract

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