Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and smokers

Carcinogenesis. 2014 Sep;35(9):2074-83. doi: 10.1093/carcin/bgu114. Epub 2014 May 23.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / virology
  • Chemokine CXCL10 / blood
  • Endogenous Retroviruses / enzymology
  • Gene Expression
  • Gene Products, gag / blood*
  • Humans
  • Interferon-gamma / blood
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / virology
  • Male
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / virology
  • RNA, Messenger / blood
  • RNA, Messenger / genetics
  • Risk Factors
  • Smoking / blood*


  • CXCL10 protein, human
  • Chemokine CXCL10
  • Gene Products, gag
  • RNA, Messenger
  • Interferon-gamma