The potential of peripheral blood HERV-K expression as a biomarker for diagnosis with prostate cancer in older men.

Abstract

5049 Background: Aberrant expression of human endogenous retrovirus-k (HERV-K) has been observed in prostate cancer (PCa). HERV-K is unique as 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. Methods: We evaluated HERV-K gag mRNA expression in PBMCs of African-American (AA) and European-American (EA) men via qRT-PCR (294 PCa cases and 135 male controls). We examined HERV-K env protein expression in PCa by immunohistochemistry. Fisher's exact test and logistic regression were used to analyze continuous and dichotomized data and calculate odds ratios (ORs). Multivariable models adjusted for age at diagnosis and race/ethnicity. Mann-Whitney test was used to compare HERV-K Ct-based expression values between groups. Results: HERV-K gag expression in PBMCs was significantly higher in PCa cases than controls (Table). Men with gag in the highest quartile had > 12-fold increased odds [OR = 12.87 (95% CI 6.3-26.25)] of PCa than those in the lowest quartile. Additionally, HERV-K may perform better in older than younger men (sensitivity of PSA testing decreases with age). HERV-K envelope protein was up-regulated in PCa, with the most abundant expression observed in AA patients (61% versus 40%, P < 0.01). Conclusions: Combining non-invasive HERV-K testing with PSA testing may improve the efficacy of PCa detection specifically among older men. Association between HERV-K gag mRNA levels in PBMC and a PCa diagnosis. Univariate analysis† Multivariable analysis* OR 95% CI P value n OR 95% CI P value n Logistic regression as a continuous variable (per Ct value) Gag mRNA 1.33 1.24-1.43 <0.0001 429 1.36 1.26-1.47 <0.0001 427 Logistic regression evaluating dose response effect** 1st Quartile 1 48 1 48 2nd Quartile 1.38 0.61-3.11 0.433 57 1.58 0.69-3.62 0.280 57 3rd Quartile 4.14 1.98-8.67 <0.0001 98 5.90 2.69-13.0 <0.0001 96 4th Quartile 12.87 6.30-26.3 <0.0001 226 17.3 8.07-37.0 <0.0001 226 Ptrend <0.0001 Ptrend <0.0001 †294 cases and 135 controls. *Adjusted for age at diagnosis and ethnicity. ***HERV-K gag levels were divided into quartiles based on control population.