title: Use of two gene panels for prostate cancer diagnosis and patient risk stratification.
abstract: Currently, no ideal prostate cancer (PCa) diagnostic or prognostic test is available due to the lack of biomarkers with high sensitivity and specificity. There is an unmet medical need to develop combinations of multiple biomarkers which may have higher accuracy in detection of PCa and stratification of aggressive and indolent cancer patients. The aim of this study was to test two biomarker gene panels in distinguishing PCa from benign prostate and high-risk, aggressive PCa from low-risk, indolent PCa, respectively. We identified a five-gene panel that can be used to distinguish PCa from benign prostate. The messenger RNA (mRNA) expression signature of the five genes was determined in 144 PCa and benign prostate specimens from prostatectomy. We showed that the five-gene panel distinguished PCa from benign prostate with sensitivity of 96.59 %, specificity of 92.86 %, and area under the curve (AUC) of 0.992 (p < 0.0001). The five-gene panel was further validated in a 137 specimen cohort and showed sensitivity of 84.62 %, specificity of 91.84 %, and AUC of 0.942 (p < 0.0001). To define subtypes of PCa for treatment guidance, we examined mRNA expression signature of an eight-gene panel in 87 PCa specimens from prostatectomy. The signature of the eight-gene panel was able to distinguish aggressive PCa (Gleason score >6) from indolent PCa (Gleason score ≤6) with sensitivity of 90.28 %, specificity of 80.00 %, and AUC of 0.967 (p < 0.0001). This panel was further validated in a 158 specimen cohort and showed significant difference between aggressive PCa and indolent PCa with sensitivity of 92.57 %, specificity of 70.00 %, and AUC of 0.962 (p < 0.0001). Our findings in assessing multiple biomarkers in combination may provide new tools to detect PCa and distinguish aggressive and indolent PCa for precision and personalized treatment. The two biomarker panels may be used in clinical settings for accurate PCa diagnosis and patient risk stratification for biomarker-guided treatment.
authors.affiliation: Department of Urology, Jinan University School of Medicine and Shenzhen People's Hospital, No. 1017, Dongmen Road North, Luo Hu District, Shenzhen, 518020, China.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Xiao
authors.affiliation: Department of Urology, Jinan University School of Medicine and Shenzhen People's Hospital, No. 1017, Dongmen Road North, Luo Hu District, Shenzhen, 518020, China.
authors.forename: Jinan
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Bio-Diagnosis, Institute of Basic Medical Sciences, 27, Taiping Road, Beijing, 100850, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Bio-Diagnosis, Institute of Basic Medical Sciences, 27, Taiping Road, Beijing, 100850, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Bio-Diagnosis, Institute of Basic Medical Sciences, 27, Taiping Road, Beijing, 100850, China.
authors.forename: Heqiu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Jinan University School of Medicine and Shenzhen People's Hospital, No. 1017, Dongmen Road North, Luo Hu District, Shenzhen, 518020, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Olympia Diagnostics, Inc., 640 W. California Ave, Suite 210, Sunnyvale, CA, 94086, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Johnson
authors.affiliation: Department of Translational Medicine, Lund University, 205 02, Malmö, Sweden. jenny_l.persson@med.lu.se.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Persson
authors.affiliation: Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Er'Lu, Guangzhou, 510080, Guangdong Province, China. chenlingwu@hotmail.com.
authors.forename: Lingwu
authors.initials: L
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D066264:Datasets as Topic; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D011467:Prostate / Q000737:chemistry; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: Aggressive prostate cancer; Indolent prostate cancer; Prostate cancer; Prostate cancer biomarkers; Prostate cancer diagnosis; Prostate cancer prognosis
references.citation: J Urol. 2015 Jul;194(1):65-72
references.pmid: 25636659
references.citation: J Urol. 2011 Jun;185(6):2119-25
references.pmid: 21496856
references.citation: Neoplasia. 2008 Nov;10(11):1285-94
references.pmid: 18953438
references.citation: J Hum Genet. 2014 Feb;59(2):78-87
references.pmid: 24284362
references.citation: Prostate Cancer Prostatic Dis. 2010 Mar;13(1):12-9
references.pmid: 19652665
references.citation: Oncotarget. 2014 Mar 15;5(5):1352-62
references.pmid: 24657880
references.citation: Clin Chem. 2006 Jun;52(6):1089-95
references.pmid: 16627561
references.citation: J Exp Clin Cancer Res. 2015 Feb 06;34:15
references.pmid: 25651917
references.citation: Br J Cancer. 2007 Mar 26;96(6):970-9
references.pmid: 17375037
references.citation: Indian J Pathol Microbiol. 2011 Jul-Sep;54(3):476-81
references.pmid: 21934206
references.citation: Genes Chromosomes Cancer. 2006 Jul;45(7):639-45
references.pmid: 16575874
references.citation: Eur J Cancer. 2009 Sep;45 Suppl 1:402-4
references.pmid: 19775647
references.citation: J Urol. 2014 Aug;192(2):409-14
references.pmid: 24508632
references.citation: Eur Urol. 2014 Sep;66(3):550-60
references.pmid: 24836057
references.citation: Neoplasia. 2006 Oct;8(10 ):885-8
references.pmid: 17059688
references.citation: Nature. 2002 Oct 10;419(6907):624-9
references.pmid: 12374981
references.citation: Cancer Res. 2008 Feb 1;68(3):645-9
references.pmid: 18245462
references.citation: Cancer Res. 2008 Apr 1;68(7):2286-91
references.pmid: 18381435
references.citation: PLoS One. 2012;7(1):e30393
references.pmid: 22272343
references.citation: BMC Cancer. 2010 Jun 22;10:315
references.pmid: 20569440
references.citation: Sci Transl Med. 2013 Sep 11;5(202):202ra122
references.pmid: 24027026
references.citation: Brief Funct Genomics. 2013 Sep;12(5):397-410
references.pmid: 23878130
references.citation: Urology. 2001 Dec;58(6 Suppl 1):25-32; discussion 32
references.pmid: 11750246
references.citation: Clin Cancer Res. 2007 Sep 1;13(17):5103-8
references.pmid: 17785564
references.citation: Eur Urol. 2000 Jun;37(6):670-4
references.pmid: 10828666
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6121-6
references.pmid: 23533275