1. Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
- Author
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Claire Rodriguez-Lafrasse, Myriam Decaussin-Petrucci, Philippe Pérot, Valérie Cheynet, Alain Ruffion, François Mallet, Guy Oriol, Nathalie Mugnier, BIOMERIEUX, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, This work was supported by bioMérieux SA, the Hospices Civils de Lyon and the French public agency OSEO (Advanced Diagnostics for New Therapeutic Approaches, a French government-funded program dedicated to personalized medicine). PP, VC, GO, NM, and FM are employees of bioMérieux SA. PP, NM and FM have submitted patent applications covering the findings of this paper, and We thank Cecile Montgiraud, Juliette Gimenez, Magali Jaillard and Bertrand Bonnaud for their contribution to the initial development and optimization of the HERV-V2 protocol. We also wish to thank Hader Haidous for his guidance on ethical considerations.
- Subjects
Male ,General Chemical Engineering ,Endogenous retrovirus ,Gene Expression ,Genome ,Transcriptome ,0302 clinical medicine ,Affymetrix ,Diagnosis ,RNA, Neoplasm ,Tumor Markers ,Cancer Biology ,Oligonucleotide Array Sequence Analysis ,MESH: Aged ,Genetics ,0303 health sciences ,MESH: Middle Aged ,General Neuroscience ,Prostate ,Middle Aged ,prostate cancer ,3. Good health ,MESH: DNA, Single-Stranded ,030220 oncology & carcinogenesis ,Medicine ,MESH: Biomarkers, Tumor ,microarray ,MESH: Endogenous Retroviruses ,PCA3 ,DNA, Complementary ,Human Endogenous Retroviruses ,NcRNA transcription ,DNA, Single-Stranded ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,ENCODE ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Biomarkers, Tumor ,Humans ,Molecular Biology ,030304 developmental biology ,Aged ,Prostatectomy ,MESH: Humans ,General Immunology and Microbiology ,Microarray analysis techniques ,Pharmacological ,Endogenous Retroviruses ,Prostatic Neoplasms ,MESH: DNA, Complementary ,MESH: RNA, Neoplasm ,Biological ,Microarray Analysis ,MESH: Male ,Retroviridae ,MESH: Prostatic Neoplasms ,MESH: Oligonucleotide Array Sequence Analysis ,Human genome ,Issue 81 ,HERV ,Biomarkers - Abstract
International audience; The prostate-specific antigen (PSA) is the main diagnostic biomarker for prostate cancer in clinical use, but it lacks specificity and sensitivity, particularly in low dosage values 1. 'How to use PSA' remains a current issue, either for diagnosis as a gray zone corresponding to a concentration in serum of 2.5-10 ng/ml which does not allow a clear differentiation to be made between cancer and noncancer 2 or for patient follow-up as analysis of post-operative PSA kinetic parameters can pose considerable challenges for their practical application 3,4. Alternatively, noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease, e.g. PCA3 in prostate cancer 5,6 and to reveal uncharacterized aspects of tumor biology. Moreover, data from the ENCODE project published in 2012 showed that different RNA types cover about 62% of the genome. It also appears that the amount of transcriptional regulatory motifs is at least 4.5x higher than the one corresponding to protein-coding exons. Thus, long terminal repeats (LTRs) of human endogenous retroviruses (HERVs) constitute a wide range of putative/candidate transcriptional regulatory sequences, as it is their primary function in infectious retroviruses. HERVs, which are spread throughout the human genome, originate from ancestral and independent infections within the germ line, followed by copy-paste propagation processes and leading to multicopy families occupying 8% of the human genome (note that exons span 2% of our genome). Some HERV loci still express proteins that have been associated with several pathologies including cancer 7-10. We have designed a high-density microarray, in Affymetrix format, aiming to optimally characterize individual HERV loci expression, in order to better understand whether they can be active, if they drive ncRNA transcription or modulate coding gene expression. This tool has been applied in the prostate cancer field (Figure 1).
- Published
- 2013