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Updated: Apr 29, 2026
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and
Tiffany A Wallace1, Ronan F Downey2, Caleb J Seufert1
1Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, Prostate Cancer Institute, Biosciences Research Building, National University of Ireland Galway, Dangan, Corrib Village, Galway, Ireland, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057-1465, USA, Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA, Department of Radiation Oncology, Galway University Hospital, Galway, Ireland and Viral Oncology, Center for Cancer and Metabolism, Stanford Research Institute International, Menlo Park, CA 94025, USA.
Abstract:
Aberrant expression of subgroup k human endogenous retroviruses (HERV-K) has been observed in prostate cancer. This subgroup is unique because it encodes sequences in the human genome containing open reading frames for near intact retroviruses. We hypothesized that HERV-K reactivation could serve as a non-invasive early disease detection marker for prostate cancer. We evaluated HERV-K gag messenger RNA (mRNA) expression in blood samples of African-American and European-American men using a case-control design via quantitative real-time PCR. Additionally, we examined HERV-K envelope protein expression in prostate tumors by immunohistochemistry. HERV-K envelope protein was commonly upregulated in prostate tumors, but more so in tumors of African-American than European-American patients (61% versus 40%, P < 0.01). Examining HERV-K gag expression in peripheral blood mononuclear cells (PBMC) from 294 cases and 135 healthy men, we found that the abundance of HERV-K gag message was significantly higher in cases than controls and was associated with increased plasma interferon-γ. Men with gag expression in the highest quartile had >12-fold increased odds {odds ratio = 12.87 [95% confidence interval 6.3-26.25]} of being diagnosed with prostate cancer than those in the lowest quartile. Moreover, our results showed that HERV-K expression may perform better as a disease biomarker in older than younger men (whereas the sensitivity of prostate-specific antigen (PSA) testing decreases with age) and in men with a smoking history compared with never smokers. Combining non-invasive HERV-K testing with PSA testing may improve the efficacy of prostate cancer detection specifically among older men and smokers who tend to develop a more aggressive disease.
Insights
Human endogenous retroviruses (HERV-K) reactivation in blood may detect early prostate cancer. Higher HERV-K gag mRNA levels significantly increase prostate cancer diagnosis odds, especially in older men and smokers.
Area of Science:
- Oncology
- Virology
- Genetics
Background:
- Aberrant expression of subgroup k human endogenous retroviruses (HERV-K) is linked to prostate cancer.
- HERV-K sequences in the human genome contain open reading frames for near-intact retroviruses.
- HERV-K reactivation is hypothesized as a potential non-invasive early detection marker for prostate cancer.
Purpose of the Study:
- To evaluate HERV-K gag messenger RNA (mRNA) expression in blood samples for prostate cancer detection.
- To examine HERV-K envelope protein expression in prostate tumors.
- To assess HERV-K's potential as an early disease biomarker, particularly in specific demographic groups.
Main Methods:
- Quantitative real-time PCR was used to measure HERV-K gag mRNA in blood samples from African-American and European-American men (294 cases, 135 controls).
- Immunohistochemistry examined HERV-K envelope protein expression in prostate tumors.
- Case-control design was employed to analyze the association between HERV-K expression and prostate cancer diagnosis.
Main Results:
- HERV-K envelope protein was upregulated in prostate tumors, more so in African-American than European-American patients (61% vs. 40%).
- HERV-K gag mRNA levels were significantly higher in prostate cancer cases than controls.
- Men in the highest quartile of HERV-K gag expression had over 12-fold increased odds of prostate cancer diagnosis (OR = 12.87).
- HERV-K expression showed potential as a biomarker in older men and smokers, outperforming PSA in older individuals.
Conclusions:
- HERV-K gag mRNA expression in PBMCs is a promising non-invasive biomarker for early prostate cancer detection.
- HERV-K expression may offer improved detection efficacy for older men and smokers, potentially complementing PSA testing.
- Targeted HERV-K testing could enhance prostate cancer screening strategies, especially for aggressive disease forms.
