title: A 2-Gene Panel Derived From Prostate Cancer-Enhanced Transcripts in Whole Blood Is Prognostic for Survival and Predicts Treatment Benefit in Metastatic Castration-Resistant Prostate Cancer.
abstract: To determine a prognostic model derived from prostate cancer-enhanced transcripts in whole blood of castration-resistant prostate cancer (CRPC) patients and explore its applicability as a surrogate of treatment response.
  
  
  
  Six out of twenty-three selected transcripts were identified as specific for detection of metastatic prostate cancer cells in peripheral blood using quantitative polymerase chain reaction (qPCR). Their prognostic value was explored in whole blood samples of a training cohort (n = 22 CRPC patients, New York, USA). A resulting 2-gene panel (2GP) including KLK2 and TMPRSS2 was validated in an independent cohort with pre- and post-treatment blood draws after 9-16 weeks of systemic treament (n = 86 CRPC patients, Munich, Germany). Overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS), and clinical PFS were analyzed. Kaplan-Meier and cox regression analyses were performed.
  
  
  
  An unfavorable 2GP (≥1 marker positive) identified patients with poor survival (median OS 10.0 months [95%CI 5.7-14.2] vs. not reached; P = 0.023). This was validated in an independent cohort at pre-treatment (median OS 7.8 [95%CI 6.5-9.2] vs. 17.3 months [95%CI 10.7-23.8]; P = 0.004) and post-treatment blood draw (median OS 5.0 [95%CI 0.0-10.0] vs. 18.0 months [95%CI 9.5-26.6]; P = 0.003). The 2GP independently predicted OS on multivariate analysis (hazard ratio 2.1 [95%CI 1.1-4.0]; P = 0.034) and performed better than PSA decline at correlation with OS. Conversion to favorable 2GP during treatment correlated with improved OS (7.8 to 20.9 months), PSA-PFS (2.8 to 12.0 months), and clinical PFS (4.6 to 8.0 months).
  
  
  
  The established 2GP is prognostic for survival at pre- and post-treatment blood draw in CRPC patients and conversion to favorable 2GP predicts treatment benefit. Prostate 76:1160-1168, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Heck
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Thalgott
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Sebastian C
authors.initials: SC
authors.lastname: Schmid
authors.affiliation: Department of Hematology/Oncology, Mount Sinai Hospital, The Tisch Cancer Institute, New York, New York.
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.affiliation: Department of Hematology/Oncology, Mount Sinai Hospital, The Tisch Cancer Institute, New York, New York.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Genetic and Genomic Sciences, The Tisch Cancer Institute, New York, New York.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Genetic and Genomic Sciences, The Tisch Cancer Institute, New York, New York.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Seitz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Desiree
authors.initials: D
authors.lastname: Porst
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Höppner
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Gschwend
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Nawroth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen
keywords: KLK2; TMPRSS2; castration-resistant prostate cancer; prognosis; transcript; whole blood