A three-gene DNA methylation biomarker accurately classifies early stage prostate cancer
Palak G. Patel PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorThomas Wessel BSc
Life Sciences Group, Thermo Fisher Scientific, Waltham, Massachusetts
Search for more papers by this authorAtsunari Kawashima MD, PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Department of Urology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Search for more papers by this authorJohn B. A. Okello PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Cardiac Genome Clinic, Ted Rogers Centre for Heart Research, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada
Search for more papers by this authorTamara Jamaspishvili MD, PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorKarl-Philippe Guérard PhD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorLaura Lee MSc
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorAnna Ying-Wah Lee PhD
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorNathan E. How MD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorDan Dion BA
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorEleonora Scarlata PhD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorChelsea L. Jackson BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorSuzanne Boursalie BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorTanya Sack BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorRachel Dunn BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorMadeleine Moussa MBBCh
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorKaren Mackie/
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorAudrey Ellis
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorElizabeth Marra
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorJoseph Chin MD
Department of Surgery (Urology), London Health Sciences Centre, London, ON, Canada
Search for more papers by this authorKhurram Siddiqui MBBS
Department of Surgery (Urology), London Health Sciences Centre, London, ON, Canada
Search for more papers by this authorKhalil Hetou MBBS
Department of Surgery (Urology), London Health Sciences Centre, London, ON, Canada
Search for more papers by this authorVinolia Arthur-Hayward
Ontario Tumor Bank, Toronto, Ontario, Canada
Search for more papers by this authorGlenn Bauman MD
Division of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Department of Physics and Astronomy, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorSimone Chevalier MD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorFadi Brimo MD
Department of Pathology, McGill University Health Center and McGill University, Montreal, Québec, Canada
Search for more papers by this authorPaul C. Boutros PhD
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
Departments of Urology and Human Genetics, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA
Search for more papers by this authorJacques Lapointe PhD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorJohn M. S. Bartlett PhD
Diagnostic Development, Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorRobert J. Gooding PhD
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Department of Physics, Engineering Physics & Astronomy, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorCorresponding Author
David M. Berman MD, PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Correspondence David M. Berman, Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, 10 Stuart St, QCRI 302A, Kingston, ON K7L 3N6, Canada.
Email: [email protected]
Search for more papers by this authorPalak G. Patel PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorThomas Wessel BSc
Life Sciences Group, Thermo Fisher Scientific, Waltham, Massachusetts
Search for more papers by this authorAtsunari Kawashima MD, PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Department of Urology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
Search for more papers by this authorJohn B. A. Okello PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Cardiac Genome Clinic, Ted Rogers Centre for Heart Research, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada
Search for more papers by this authorTamara Jamaspishvili MD, PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorKarl-Philippe Guérard PhD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorLaura Lee MSc
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorAnna Ying-Wah Lee PhD
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorNathan E. How MD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorDan Dion BA
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorEleonora Scarlata PhD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorChelsea L. Jackson BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorSuzanne Boursalie BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorTanya Sack BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorRachel Dunn BSc
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorMadeleine Moussa MBBCh
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorKaren Mackie/
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorAudrey Ellis
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorElizabeth Marra
Division of Surgical Pathology, Departmant of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada
Search for more papers by this authorJoseph Chin MD
Department of Surgery (Urology), London Health Sciences Centre, London, ON, Canada
Search for more papers by this authorKhurram Siddiqui MBBS
Department of Surgery (Urology), London Health Sciences Centre, London, ON, Canada
Search for more papers by this authorKhalil Hetou MBBS
Department of Surgery (Urology), London Health Sciences Centre, London, ON, Canada
Search for more papers by this authorVinolia Arthur-Hayward
Ontario Tumor Bank, Toronto, Ontario, Canada
Search for more papers by this authorGlenn Bauman MD
Division of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, Ontario, Canada
Department of Physics and Astronomy, University of Western Ontario, London, Ontario, Canada
Search for more papers by this authorSimone Chevalier MD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorFadi Brimo MD
Department of Pathology, McGill University Health Center and McGill University, Montreal, Québec, Canada
Search for more papers by this authorPaul C. Boutros PhD
Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
Departments of Urology and Human Genetics, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA
Search for more papers by this authorJacques Lapointe PhD
Division of Urology, Department of Surgery, McGill University and the Research Institute of the McGill University Health Centre, Montreal, Québec, Canada
Search for more papers by this authorJohn M. S. Bartlett PhD
Diagnostic Development, Ontario Institute for Cancer Research (OICR), Toronto, Ontario, Canada
Search for more papers by this authorRobert J. Gooding PhD
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Department of Physics, Engineering Physics & Astronomy, Queen's University, Kingston, Ontario, Canada
Search for more papers by this authorCorresponding Author
David M. Berman MD, PhD
Department of Pathology & Molecular Medicine, Queen's University, Kingston, Ontario, Canada
Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada
Correspondence David M. Berman, Division of Cancer Biology & Genetics, Queen's Cancer Research Institute, Queen's University, 10 Stuart St, QCRI 302A, Kingston, ON K7L 3N6, Canada.
Email: [email protected]
Search for more papers by this authorAbstract
Background
We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations.
Materials and methods
We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real-time methylation-specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated.
Results
In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S-transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest-specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation.
Conclusion
We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three-gene biomarker represents a promising basis for more accurate prostate cancer diagnosis.
CONFLICT OF INTERESTS
The authors declare that there is no conflict of interests.
Supporting Information
| Filename | Description |
|---|---|
| pros23895-sup-0001-Patel_et_al-The_Prostate_Supporting_Info_Final_July072019.doc225 KB | Supporting information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Brawley OW. Trends in prostate cancer in the United States. JNCI Monographs. 2012; 2012(45): 152-156. https://doi.org/10.1093/jncimonographs/lgs035
10.1093/jncimonographs/lgs035 Google Scholar
- 2Delongchamps NB, de la Roza G, Jones R, Jumbelic M, Haas GP. Saturation biopsies on autopsied prostates for detecting and characterizing prostate cancer. BJU Int. 2009; 103(1): 49-54. https://doi.org/10.1111/j.1464-410X.2008.07900.x
- 3Haas GP, Delongchamps N, Brawley OW, Wang CY, de la Roza G. The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. Can J Urol. 2008; 15(1): 3866-3871.
- 4Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized european study. N Engl J Med. 2009; 360(13): 1320-1328. https://doi.org/10.1056/NEJMoa0810084
- 5Wolf AMD, Wender RC, Etzioni RB, et al. American cancer society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010; 60(2): 70-98. https://doi.org/10.3322/caac.20066
- 6Aubry W, Lieberthal R, Willis A, Bagley G, Willis SM, Layton A. Budget impact model: epigenetic assay can help avoid unnecessary repeated prostate biopsies and reduce healthcare spending. Am Health Drug Benefits. 2013; 6(1): 15-24.
- 7Tokheim CJ, Papadopoulos N, Kinzler KW, Vogelstein B, Karchin R. Evaluating the evaluation of cancer driver genes. Proc Natl Acad Sci. 2016; 113(50): 14330-14335. https://doi.org/10.1073/pnas.1616440113
- 8Rizzardi AE, Rosener NK, Koopmeiners JS, et al. Evaluation of protein biomarkers of prostate cancer aggressiveness. BMC Cancer. 2014; 14: 244. https://doi.org/10.1186/1471-2407-14-244
- 9Wang L-Y, Cui J-J, Zhu T, et al. Biomarkers identified for prostate cancer patients through genome-scale screening. Oncotarget. 2017; 8(54): 92055-92063. https://doi.org/10.18632/oncotarget.20739
- 10Souza MF, Kuasne H, Barros-Filho MC, et al. Circulating mRNAs and miRNAs as candidate markers for the diagnosis and prognosis of prostate cancer. PLoS One. 2017; 12(9):e0184094. https://doi.org/10.1371/journal.pone.0184094
- 11Alford AV, Brito JM, Yadav KK, Yadav SS, Tewari AK, Renzulli J. The use of biomarkers in prostate cancer screening and treatment. Rev Urol. 2017; 19(4): 221-234. https://doi.org/10.3909/riu0772
- 12Gaudreau P-O, Stagg J, Soulières D, Saad F. The present and future of biomarkers in prostate cancer: proteomics, genomics, and immunology advancements. Biomark Cancer. 2016; 8s2(Suppl 2): BIC.S31802. https://doi.org/10.4137/BIC.S31802
10.4137/BIC.S31802 Google Scholar
- 13Kohaar I, Petrovics G, Srivastava S. A rich array of prostate cancer molecular biomarkers: opportunities and challenges. Int J Mol Sci. 2019; 20(8): 1813. https://doi.org/10.3390/ijms20081813
- 14Ngollo M, Dagdemir A, Karsli-Ceppioglu S, et al. Epigenetic modifications in prostate cancer. Epigenomics. 2014; 6(4): 415-426. https://doi.org/10.2217/epi.14.34
- 15Strand S, Orntoft T, Sorensen K. Prognostic DNA methylation markers for prostate cancer. Int J Mol Sci. 2014; 15(9): 16544-16576. https://doi.org/10.3390/ijms150916544
- 16Lee WH, Morton RA, Epstein JI, et al. Cytidine methylation of regulatory sequences near the pi-class glutathione S-transferase gene accompanies human prostatic carcinogenesis. Proc Natl Acad Sci. 1994; 91(24): 11733-11737. https://doi.org/10.1073/pnas.91.24.11733
- 17Lee WH, Isaacs WB, Bova GS, Nelson WG. CG island methylation changes near the GSTP1 gene in prostatic carcinoma cells detected using the polymerase chain reaction: a new prostate cancer biomarker. Cancer Epidemiol Prev Biomark. 1997; 6(6): 443-450.
- 18Cairns P, Esteller M, Herman JG, et al. Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. Clin Cancer Res. 2001; 7(9): 2727-2730.
- 19Yegnasubramanian S, Kowalski J, Gonzalgo ML, et al. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res. 2004; 64(6): 1975-1986.
- 20Aryee MJ, Liu W, Engelmann JC, et al. DNA methylation alterations exhibit intraindividual stability and interindividual heterogeneity in prostate cancer metastases. Sci Transl Med. 2013; 5(169): 169ra10. https://doi.org/10.1126/scitranslmed.3005211
- 21Haldrup C, Mundbjerg K, Vestergaard EM, et al. DNA methylation signatures for prediction of biochemical recurrence after radical prostatectomy of clinically localized prostate cancer. J Clin Oncol. 2013; 31(26): 3250-3258. https://doi.org/10.1200/JCO.2012.47.1847
- 22Roupret M, Hupertan V, Yates DR, et al. Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage. Clin Cancer Res. 2007; 13(6): 1720-1725. https://doi.org/10.1158/1078-0432.CCR-06-2467
- 23Ge Y-Z, Xu L-W, Jia R-P, et al. The association between RASSF1A promoter methylation and prostate cancer: evidence from 19 published studies. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014; 35(4): 3881-3890. https://doi.org/10.1007/s13277-013-1515-3
- 24Kobayashi Y, Absher DM, Gulzar ZG, et al. DNA methylation profiling reveals novel biomarkers and important roles for DNA methyltransferases in prostate cancer. Genome Res. 2011; 21(7): 1017-1027. https://doi.org/10.1101/gr.119487.110
- 25Mahapatra S, Klee EW, Young CYF, et al. Global methylation profiling for risk prediction of prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2012; 18(10): 2882-2895. https://doi.org/10.1158/1078-0432.CCR-11-2090
- 26Fraser M, Sabelnykova VY, Yamaguchi TN, et al. Genomic hallmarks of localized, nonindolent prostate cancer. Nature. 2017; 541(7637): 359-364. https://doi.org/10.1038/nature20788
- 27Ruggero K, Farran-Matas S, Martinez-Tebar A, Aytes A. Epigenetic regulation in prostate cancer progression. Curr Mol Biol Rep. 2018; 4(2): 101-115. https://doi.org/10.1007/s40610-018-0095-9
- 28Vanaja DK, Ehrich M, Van den Boom D, et al. Hypermethylation of genes for diagnosis and risk stratification of prostate cancer. Cancer Invest. 2009; 27(5): 549-560. https://doi.org/10.1080/07357900802620794
- 29Perry AS, Watson RWG, Lawler M, Hollywood D. The epigenome as a therapeutic target in prostate cancer. Nat Rev Urol. 2010; 7(12): 668-680. https://doi.org/10.1038/nrurol.2010.185
- 30Valdés-Mora F, Clark SJ. Prostate cancer epigenetic biomarkers: next-generation technologies. Oncogene. 2015; 34(13): 1609-1618. https://doi.org/10.1038/onc.2014.111
- 31Lin P-C, Giannopoulou EG, Park K, et al. Epigenomic alterations in localized and advanced prostate cancer. Neoplasia. 2013; 15(4): 373-IN5.
- 32Partin AW, Van Neste L, Klein EA, et al. Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. J Urol. 2014; 192(4): 1081-1087. https://doi.org/10.1016/j.juro.2014.04.013
- 33Stewart GD, Van Neste L, Delvenne P, et al. Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol. 2013; 189(3): 1110-1116. https://doi.org/10.1016/j.juro.2012.08.219
- 34Van Neste L, Hendriks RJ, Dijkstra S, et al. Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score. Eur Urol. 2016; 70(5): 740-748. https://doi.org/10.1016/j.eururo.2016.04.012
- 35Haese A, Trooskens G, Steyaert S, et al. Multicenter optimization and validation of a 2-gene mRNA urine test for detection of clinically significant prostate cancer before initial prostate biopsy. J Urol. 2019; 202: 256-263. https://doi.org/10.1097/JU.0000000000000293
- 36 Health Quality Ontario. Prolaris cell cycle progression test for localized prostate cancer: a health technology assessment. Ont Health Technol Assess Ser. 2017; 17(6): 1-75.
- 37Klein EA, Cooperberg MR, Magi-Galluzzi C, et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol. 2014; 66(3): 550-560. https://doi.org/10.1016/j.eururo.2014.05.004
- 38Ioannidis JPA, Bossuyt PMM. Waste, leaks, and failures in the biomarker pipeline. Clin Chem. 2017; 63(5): 963-972. https://doi.org/10.1373/clinchem.2016.254649
- 39Ransohoff DF. Challenges and opportunities in evaluating diagnostic tests. J Clin Epidemiol. 2002; 55(12): 1178-1182.
- 40Ioannidis JPA. Biomarker failures. Clin Chem. 2013; 59(1): 202-204. https://doi.org/10.1373/clinchem.2012.185801
- 41Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A. 1996; 93(18): 9821-9826.
- 42Huang Z, Bassil CF, Murphy SK. Methods in molecular biology: methods and protocols. Methods Mol Biol Clifton NJ. 2013; 1049: 75-82. https://doi.org/10.1007/978-1-62703-547-7_7
- 43Ku J-L, Jeon Y-K, Park J-G. Methods in molecular biology. Methods Mol Biol Clifton NJ. 2011; 791: 23-32. https://doi.org/10.1007/978-1-61779-316-5_3
- 44Olkhov-Mitsel E, Zdravic D, Kron K, van der Kwast T, Fleshner N, Bapat B. Novel multiplex methylight protocol for detection of DNA methylation in patient tissues and bodily fluids. Sci Rep. 2014; 4: 4432. https://doi.org/10.1038/srep04432
- 45Patel P, Selvarajah S, Boursalie S, et al. Extraction of Both RNA and DNA from formalin-fixed paraffin embedded tissue cores | protocol. J Vis Exp JoVE. 2016;(114), https://doi.org/10.3791/54299
- 46Ongenaert M, Van Neste L, De Meyer T, Menschaert G, Bekaert S, Van Criekinge W. PubMeth: a cancer methylation database combining text-mining and expert annotation. Nucleic Acids Res. 2007; 36(suppl_1): D842-D846. https://doi.org/10.1093/nar/gkm788
- 47Weisenberger DJ. Analysis of repetitive element DNA methylation by MethyLight. Nucleic Acids Res. 2005; 33(21): 6823-6836. https://doi.org/10.1093/nar/gki987
- 48Bustin SA, Benes V, Garson JA, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009; 55(4): 611-622. https://doi.org/10.1373/clinchem.2008.112797
- 49Patel PG, Selvarajah S, Guérard K-P, et al. Reliability and performance of commercial RNA and DNA extraction kits for FFPE tissue cores. PLoS One. 2017; 12(6):e0179732. https://doi.org/10.1371/journal.pone.0179732.
- 50Pfaffl MW. A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res. 2001; 29(9): 45e-45e.
- 51Bonferroni C. Teoria statistica delle classi e calcolo delle probabilita. Pubblicazioni R Ist Super Sci Econ E Commericiali Firenze. 1936; 8: 3-62.
- 52 R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2017.
- 53Robin X, Turck N, Hainard A, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011; 12: 77. https://doi.org/10.1186/1471-2105-12-77
- 54Slowikowski Kamil. Ggrepel: Repulsive Text and Label Geoms for “Ggplot2.”; 2017.
- 55Wickham H. Ggplot2: Elegant Graphics for Data Analysis. New York: Springer-Verlag; 2009.
- 56 The Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell. 2015; 163(4): 1011-1025. https://doi.org/10.1016/j.cell.2015.10.025
- 57Bhasin JM, Lee BH, Matkin L, et al. Methylome-wide sequencing detects DNA hypermethylation distinguishing indolent from aggressive prostate cancer. Cell Rep. 2015; 13(10): 2135-2146. https://doi.org/10.1016/j.celrep.2015.10.078
- 58Bhasin JM, Hu B, Ting AH. MethylAction: detecting differentially methylated regions that distinguish biological subtypes. Nucleic Acids Res. 2016; 44(1): 106-116. https://doi.org/10.1093/nar/gkv1461
- 59Gaspar JM, Hart RP. DMRfinder: efficiently identifying differentially methylated regions from MethylC-seq data. BMC Bioinformatics. 2017; 18: 18. https://doi.org/10.1186/s12859-017-1909-0
- 60Wu H, Xu T, Feng H, et al. Detection of differentially methylated regions from whole-genome bisulfite sequencing data without replicates. Nucleic Acids Res. 2015; 43(21): gkv715. https://doi.org/10.1093/nar/gkv715
- 61Ahmed H. Promoter methylation in prostate cancer and its application for the early detection of prostate cancer using serum and urine samples. Biomark Cancer. 2010; 2: BIC.S3187. https://doi.org/10.4137/BIC.S3187
10.4137/BIC.S3187 Google Scholar
- 62Costa VL, Henrique R, Jerónimo C. Epigenetic markers for molecular detection of prostate cancer. Dis Markers. 2007; 23(1-2): 31-41. https://doi.org/10.1155/2007/356742
- 63Hopkins TG, Burns PA, Routledge MN. DNA Methylation of GSTP1 as biomarker in diagnosis of prostate cancer. Urology. 2007; 69(1): 11-16. https://doi.org/10.1016/j.urology.2006.10.008
- 64Kang GH, Lee S, Lee HJ, Hwang KS. Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia. J Pathol. 2004; 202(2): 233-240. https://doi.org/10.1002/path.1503
- 65Mehrotra J, Varde S, Wang H, et al. Quantitative, spatial resolution of the epigenetic field effect in prostate cancer. Prostate. 2008; 68(2): 152-160. https://doi.org/10.1002/pros.20675
- 66Wu T, Giovannucci E, Welge J, Mallick P, Tang W-Y, Ho S-M. Measurement of GSTP1 promoter methylation in body fluids may complement PSA screening: a meta-analysis. Br J Cancer. 2011; 105(1): 65-73. https://doi.org/10.1038/bjc.2011.143
- 67Chunhua L, Zhao H, Zhao H, et al. Clinical significance of peripheral blood PCA3 gene expression in early diagnosis of prostate cancer. Transl Oncol. 2018; 11(3): 628-632. https://doi.org/10.1016/j.tranon.2018.02.019
- 68Deras IL, Aubin SMJ, Blase A, et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol. 2008; 179(4): 1587-1592. https://doi.org/10.1016/j.juro.2007.11.038
- 69Gittelman MC, Hertzman B, Bailen J, et al. PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. J Urol. 2013; 190(1): 64-69. https://doi.org/10.1016/j.juro.2013.02.018
- 70Møller M, Strand SH, Mundbjerg K, et al. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients. Sci Rep. 2017; 7: 40636. https://doi.org/10.1038/srep40636
- 71Martignano F, Gurioli G, Salvi S, et al. GSTP1 methylation and protein expression in prostate cancer: diagnostic implications. Dis Markers. 2016; 2016: 1-6. https://doi.org/10.1155/2016/4358292
- 72Henrique R, Jerónimo C. Molecular detection of prostate cancer: a role for GSTP1 hypermethylation. Eur Urol. 2004; 46(5): 660-669. https://doi.org/10.1016/j.eururo.2004.06.014 discussion 669
- 73Srivastava S, Kramer BS. Validation: a critical step in bringing biomarkers to clinical fruition. Ann Epidemiol. 2018; 28(2): 135-138. https://doi.org/10.1016/j.annepidem.2017.10.013
- 74Zapała P, Dybowski B, Poletajew S, Radziszewski P. What can be expected from prostate cancer biomarkers a clinical perspective. Urol Int. 2018; 100(1): 1-12. https://doi.org/10.1159/000479982
- 75Massie CE, Mills IG, Lynch AG. The importance of DNA methylation in prostate cancer development. J Steroid Biochem Mol Biol. 2017; 166: 1-15. https://doi.org/10.1016/j.jsbmb.2016.04.009
- 76Esteller M. Epigenetics in cancer. N Engl J Med. 2008; 358(11): 1148-1159. https://doi.org/10.1056/NEJMra072067
- 77Taby R, Issa JPJ. Cancer epigenetics. CA Cancer J Clin. 2010; 60(6): 376-392. https://doi.org/10.3322/caac.20085
- 78Wu Y, Sarkissyan M, Vadgama JV. Methods in molecular biology. Methods Mol Biol Clifton NJ. 2015; 1238: 425-466. https://doi.org/10.1007/978-1-4939-1804-1_23
- 79Singh S. Cytoprotective and regulatory functions of glutathione S-transferases in cancer cell proliferation and cell death. Cancer Chemother Pharmacol. 2015; 75(1): 1-15. https://doi.org/10.1007/s00280-014-2566-x
- 80Bastian PJ, Yegnasubramanian S, Palapattu GS, et al. Molecular biomarker in prostate cancer: the role of CpG island hypermethylation. Eur Urol. 2004; 46(6): 698-708. https://doi.org/10.1016/j.eururo.2004.07.022
- 81Greene KL, Li L-C, Okino ST, Carroll PR. Chapter 33—Molecular Basis Of Prostate Cancer. In: J Mendelsohn, PM Howley, MA Israel, JW Gray, CB Thompson, eds. The Molecular Basis of Cancer. Third Edition. Philadelphia: W.B. Saunders; 2008: 431-440. https://doi.org/10.1016/B978-141603703-3.10033-0
10.1016/B978-141603703-3.10033-0 Google Scholar
- 82Knudsen BS, Vasioukhin V. Chapter 1—Mechanisms of Prostate Cancer Initiation and Progression. In: GF Vande Woude, G Klein, eds. Advances in Cancer Research. 109. Oxford, UK: Academic Press; 2010: 1-50. https://doi.org/10.1016/B978-0-12-380890-5.00001-6
- 83Kou X, Chen N, Feng Z, Luo L, Yin Z. GSTP1 negatively regulates Stat3 activation in epidermal growth factor signaling. Oncol Lett. 2013; 5(3): 1053-1057. https://doi.org/10.3892/ol.2012.1098
- 84Abdulghani J, Gu L, Dagvadorj A, et al. Stat3 promotes metastatic progression of prostate cancer. Am J Pathol. 2008; 172(6): 1717-1728. https://doi.org/10.2353/ajpath.2008.071054
- 85Shiozawa Y, Pedersen EA, Patel LR, et al. GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche. Neoplasia. 2010; 12(2): 116-127.
- 86Sainaghi PP, Castello L, Bergamasco L, Galletti M, Bellosta P, Avanzi GC. Gas6 induces proliferation in prostate carcinoma cell lines expressing the Axl receptor. J Cell Physiol. 2005; 204(1): 36-44. https://doi.org/10.1002/jcp.20265
- 87Wu G, Ma Z, Hu W. Molecular insights of Gas6/TAM in cancer development and therapy. Cell Death Dis. 2017; 8(3):e2700. https://doi.org/10.1038/cddis.2017.113
- 88Spicer AP, Joo A, Bowling RA. A hyaluronan binding link protein gene family whose members are physically linked adjacent to chrondroitin sulfate proteoglycan core protein genes: the missing links. J Biol Chem. 2003; 278(23): 21083-21091. https://doi.org/10.1074/jbc.M213100200
- 89Huynh M, Pak C, Markovina S, et al. Hyaluronan and proteoglycan link protein 1 (HAPLN1) activates bortezomib-resistant NF-κB activity and increases drug resistance in multiple myeloma. J Biol Chem. 2018; 293(7): 2452-2465. https://doi.org/10.1074/jbc.RA117.000667
- 90Altintas Z, Tothill IE. Molecular biosensors: promising new tools for early detection of cancer. Nanobiosensors in Disease Diagnosis. 2015; 4: 1-10. https://doi.org/10.2147/NDD.S56772
- 91Leygo C, Williams M, Jin HC, et al. DNA methylation as a noninvasive epigenetic biomarker for the detection of cancer. Dis Markers. 2017; 2017: 1-13. https://doi.org/10.1155/2017/3726595
- 92Carroll PH, Mohler JL. NCCN guidelines updates: prostate cancer and prostate cancer early detection. J Natl Compr Cancer Netw JNCCN. 2018; 16(5S): 620-623. https://doi.org/10.6004/jnccn.2018.0036
- 93Mohler JL, Antonarakis ES, Armstrong AJ, et al. Prostate cancer, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw JNCCN. 2019; 17(5): 479-505. https://doi.org/10.6004/jnccn.2019.0023
- 94D'Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998; 280(11): 969-974.
- 95Taylor RA, Fraser M, Livingstone J, et al. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nat Commun. 2017; 8: 13671. https://doi.org/10.1038/ncomms13671
- 96Shaikh SA. Measures derived from a 2 x 2 table for an accuracy of a diagnostic test. J Biom Biostat. 2011; 02(5): 1-4. https://doi.org/10.4172/2155-6180.1000128
10.4172/2155-6180.1000128 Google Scholar
