Document Type : Original Article


1 Department of Biological Systems Engineering, College of Agricultural, Human, and Natural Resource Sciences, Washington State University, Washington, USA

2 Department of Genetics, China Pharmaceutical University, Nanjing, Jiangsu, China

3 Department of Mathematics, Zhejiang Chinese Medical University, Zhejiang, China

4 Department of Biotechnology, Pramukh Swami Science & H. D. Patel Arts College, Kadi HNGU University, Patan, India


Breast cancer is one of the most common cancers known, and it is also a significant cause of death in women. If breast cancer is diagnosed in the early stages of the disease and treated appropriately, we can see an increase in life expectancy for more than 90% of patients. Research on molecular biomarkers with enough sensitivity and specificity can be a good solution for rapid diagnosis in the clinical stage. Meanwhile, endogenous retroviral biomarkers can have good functional benefits. Human Endogenous Retroviruses as heterochromatin fragments of the genome usually lack expression, but in several types of human cancers, including breast cancer, HERV-Kenv mRNA is significantly increased. This study used RT-PCR to detect the expression of HERV-K mRNA and tried to introduce screening tools for the early detection of breast cancer. In this case-control study, blood samples of 50 patients with hospitalized breast cancer and 50 healthy individuals were designed to evaluate the expression of HERV-Kenv mRNA using specific primers and were analyzed by RT-PCR. PCR test was optimized as a positive control using Hela cancer cell line (cervical adenocarcinoma), which expresses the HERV-Kenv gene. Studies on both patient and control groups showed that the increase in mRNA expression was positive in 64% of patients with breast cancer and negative in all healthy individuals. The results indicate an increase in the expression of endogenous human retroviruses (HERVs) in breast cancer. Because the amount of HERV-Kenv mRNA in the blood of breast cancer patients increases dramatically, it is predicted that these mobile genetic elements could be used as a diagnostic biomarker.

Graphical Abstract

Association between Human Endogenous Retrovirus K gene expression and breast cancer


Main Subjects

Selected authors of this article by journal


ِDr. Masoud Tourang
Washington State University
ِDr. Ramchandra Suthar
Kadi HNGU University


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  1. Yu K, Tan L, Lin L, Cheng X, Yi Z, Sato T (2021) Deep-learning-empowered breast cancer auxiliary diagnosis for 5GB remote E-health. IEEE Wireless Communications 28(3):54-61. doi:
  2. Hu C, Hart SN, Gnanaolivu R, Huang H, Lee KY, Na J, Gao C, Lilyquist J, Yadav S, Boddicker NJ (2021) A Population-Based Study of Genes Previously Implicated in Breast Cancer. New England Journal of Medicine 384(5):440-451. doi:
  3. Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q (2021) Breast Cancer Risk Genes-Association Analysis in More than 113,000 Women. N Engl J Med):428-439. doi:
  4. Pasha N, Turner NC (2021) Understanding and overcoming tumor heterogeneity in metastatic breast cancer treatment. Nature Cancer):1-13. doi:
  5. Freelander A, Brown LJ, Parker A, Segara D, Portman N, Lau B, Lim E (2021) Molecular Biomarkers for Contemporary Therapies in Hormone Receptor-Positive Breast Cancer. Genes 12(2):285. doi:
  6. Gamble P, Jaroensri R, Wang H, Tan F, Moran M, Brown T, Flament-Auvigne I, Rakha EA, Toss M, Dabbs DJ (2021) Determining breast cancer biomarker status and associated morphological features using deep learning. Communications Medicine 1(1):1-12. doi:
  7. Steely CJ, Russell KL, Feusier JE, Qiao Y, Tavtigian SV, Marth G, Jorde LB (2021) Mobile element insertions and associated structural variants in longitudinal breast cancer samples. Scientific Reports 11(1):1-12. doi:
  8. Kojima S, Yoshikawa K, Ito J, Nakagawa S, Parrish NF, Horie M, Kawano S, Tomonaga K (2021) Virus-like insertions with sequence signatures similar to those of endogenous nonretroviral RNA viruses in the human genome. Proceedings of the National Academy of Sciences 118(5). doi:
  9. Song Y, Li X, Wei X, Cui J (2021) Human Endogenous Retroviruses as Biomedicine Markers. Virologica Sinica):1-7. doi:
  10. Shah AH, Gilbert M, Ivan ME, Komotar RJ, Heiss J, Nath A (2021) The role of human endogenous retroviruses in gliomas: from etiological perspectives and therapeutic implications. Neuro-oncology). doi:
  11. Grandi N, Pisano MP, Pessiu E, Scognamiglio S, Tramontano E (2021) HERV-K (HML7) Integrations in the Human Genome: Comprehensive Characterization and Comparative Analysis in Non-Human Primates. Biology 10(5):439. doi:
  12. Chiu ES, VandeWoude S (2021) Endogenous retroviruses drive resistance and promotion of exogenous retroviral homologs. Annual Review of Animal Biosciences 9:225-248. doi:
  13. Arru G, Galleri G, Deiana GA, Zarbo IR, Sechi E, Bo M, Cadoni MPL, Corda DG, Frau C, Simula ER (2021) HERV-K Modulates the Immune Response in ALS Patients. Microorganisms 9(8):1784. doi:
  14. Gao Y, Yu X-F, Chen T (2021) Human endogenous retroviruses in cancer: Expression, regulation and function. Oncology Letters 21(2):1-1. doi:
  15. Khan AS, Muller J, Sears J (2001) Early detection of endogenous retroviruses in chemically induced mouse cells. Virus research 79(1-2):39-45. doi:
  16. Gabriel U, Steidler A, Trojan L, Michel MS, Seifarth W, Fabarius A (2010) Smoking increases transcription of human endogenous retroviruses in a newly established in vitro cell model and in normal urothelium. AIDS research and human retroviruses 26(8):883-888. doi:
  17. Garson JA, Usher L, Al-Chalabi A, Huggett J, Day EF, McCormick AL (2019) Quantitative analysis of human endogenous retrovirus-K transcripts in postmortem premotor cortex fails to confirm elevated expression of HERV-K RNA in amyotrophic lateral sclerosis. Acta neuropathologica communications 7(1):1-9. doi:
  18. Mayer J, Harz C, Sanchez L, Pereira GC, Maldener E, Heras SR, Ostrow LW, Ravits J, Batra R, Meese E (2018) Transcriptional profiling of HERV-K (HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins. Molecular neurodegeneration 13(1):1-25. doi:
  19. Neulinger-Muñoz M, Schaack D, Grekova SP, Bauer AS, Giese T, Salg GA, Espinet E, Leuchs B, Heller A, Nüesch JP (2021) Human Retrotransposons and the Global Shutdown of Homeostatic Innate Immunity by Oncolytic Parvovirus H-1PV in Pancreatic Cancer. Viruses 13(6):1019. doi:
  20. Waks AG, Winer EP (2019) Breast cancer treatment: a review. Jama 321(3):288-300. doi:10.1001/jama.2018.19323
  21. McKinney SM, Sieniek M, Godbole V, Godwin J, Antropova N, Ashrafian H, Back T, Chesus M, Corrado GS, Darzi A (2020) International evaluation of an AI system for breast cancer screening. Nature 577(7788):89-94. doi:
  22. Loyez M, Lobry M, Hassan EM, DeRosa MC, Caucheteur C, Wattiez R (2021) HER2 breast cancer biomarker detection using a sandwich optical fiber assay. Talanta 221:121452. doi:
  23. Tavakolian S, Goudarzi H, Faghihloo E (2019) Evaluating the expression level of HERV-K env, np9, rec and gag in breast tissue. Infectious agents and cancer 14(1):1-5. doi:
  24. Ko E-J, Song KS, Ock MS, Choi YH, Kim S, Kim H-S, Cha H-J (2021) Expression profiles of human endogenous retrovirus (HERV)-K and HERV-R Env proteins in various cancers. BMB reports 54(7):368. doi:
  25. Wang‐Johanning F, Liu J, Rycaj K, Huang M, Tsai K, Rosen DG, Chen DT, Lu DW, Barnhart KF, Johanning GL (2007) Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer. International journal of cancer 120(1):81-90. doi:
  26. Golan M, Hizi A, Resau JH, Yaal-Hahoshen N, Reichman H, Keydar I, Tsarfaty I (2008) Human endogenous retrovirus (HERV-K) reverse transcriptase as a breast cancer prognostic marker. Neoplasia 10(6):521-IN522. doi:
  27. Zhao J, Rycaj K, Geng S, Li M, Plummer JB, Yin B, Liu H, Xu X, Zhang Y, Yan Y (2011) Expression of human endogenous retrovirus type K envelope protein is a novel candidate prognostic marker for human breast cancer. Genes & cancer 2(9):914-922. doi:
  28. Rhyu D-W, Kang Y-J, Ock M-S, Eo J-W, Choi Y-H, Kim W-J, Leem S-H, Yi J-M, Kim H-S, Cha H-J (2014) Expression of human endogenous retrovirus env genes in the blood of breast cancer patients. International journal of molecular sciences 15(6):9173-9183. doi:
  29. Wang‐Johanning F, Li M, Esteva FJ, Hess KR, Yin B, Rycaj K, Plummer JB, Garza JG, Ambs S, Johanning GL (2014) Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early‐stage breast cancer. International journal of cancer 134(3):587-595. doi: