Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein Journal Article

Authors: Reis, B. S.; Jungbluth, A. A.; Frosina, D.; Holz, M.; Ritter, E.; Nakayama, E.; Ishida, T.; Obata, Y.; Carver, B.; Scher, H.; Scardino, P. T.; Slovin, S.; Subudhi, S. K.; Reuter, V. E.; Savage, C.; Allison, J. P.; Melamed, J.; Jäager, E.; Ritter, G.; Old, L. J.; Gnjatic, S.
Article Title: Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein
Abstract: Purpose: Human endogenous retroviruses (HERV) encode 8% of the human genome. While HERVs may play a role in autoimmune and neoplastic disease, no mechanistic association has yet been established. We studied the expression and immunogenicity of a HERV-K GAG protein encoded on chromosome 22q11.23 in relation to the clinical course of prostate cancer. Experimental Design: In vitro expression of GAG-HERV-K was analyzed in panels of normal and malignant tissues, microarrays, and cell lines, and effects of demethylation and androgen stimulation were evaluated. Patient sera were analyzed for seroreactivity to GAG-HERV-K and other self-antigens by ELISA and seromics (protein array profiling). Results: GAG-HERV-K expression was most frequent in prostate tissues and regulated both by demethylation of the promoter region and by androgen stimulation. Serum screening revealed that antibodies to GAG-HERV-K are found in a subset of patients with prostate cancer (33 of 483, 6.8%) but rarely in male healthy donors (1 of 55, 1.8%). Autoantibodies to GAG-HERV-K occurred more frequently in patients with advanced prostate cancer (29 of 191 in stage III-IV, 21.0%) than in early prostate cancer (4 of 292 in stages I-II, 1.4%). Presence of GAG-HERV-K serum antibody was correlated with worse survival of patients with prostate cancer, with a trend for faster biochemical recurrence in patients with antibodies to GAG-HERV-K. Conclusions: Preferential expression of GAG-HERV-K ch22q11.23 in prostate cancer tissue and increased frequency of autoantibodies observed in patients with advanced prostate cancer make this protein one of the first bona fide retroviral cancer antigens in humans, with potential as a biomarker for progression and biochemical recurrence rate of prostate cancer. © 2013 American Association for Cancer Research.
Journal Title: Clinical Cancer Research
Volume: 19
Issue: 22
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2013-11-15
Start Page: 6112
End Page: 6125
Language: English
DOI: 10.1158/1078-0432.ccr-12-3580
PROVIDER: scopus
PUBMED: 24081977
Notes: Export Date: 2 January 2014 -- CODEN: CCREF -- Source: Scopus
Altmetric Score
MSK Authors
  1. Caroline Savage
    80 Savage
  2. Susan Slovin
    184 Slovin
  3. Peter T Scardino
    620 Scardino
  4. Sumit Kumar Subudhi
    10 Subudhi
  5. Bernardo Sgarbi Chaves Reis
    1 Reis
  6. James P Allison
    128 Allison
  7. Brett Stewart Carver
    109 Carver
  8. Sacha Gnjatic
    111 Gnjatic
  9. Achim Jungbluth
    337 Jungbluth
  10. Gerd Ritter
    156 Ritter
  11. Erika Ritter
    34 Ritter
  12. Victor Reuter
    898 Reuter
  13. Howard Scher
    816 Scher
  14. Lloyd J Old
    381 Old
  15. Denise Frosina
    82 Frosina
  16. Megan Holz
    5 Holz