Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence.
Prostate cancer remains the second leading cause of cancer death in American men and there is an unmet need for biomarkers to identify patients with aggressive disease. In an effort to identify biomarkers of recurrence, we performed global RNA sequencing on 106 formalin-fixed, paraffin-embedded prostatectomy samples from 100 patients at three independent sites, defining a 24-gene signature panel. The 24 genes in this panel function in cell-cycle progression, angiogenesis, hypoxia, apoptosis, PI3K signaling, steroid metabolism, translation, chromatin modification, and transcription. Sixteen genes have been associated with cancer, with five specifically associated with prostate cancer (BTG2, IGFBP3, SIRT1, MXI1, and FDPS). Validation was performed on an independent publicly available dataset of 140 patients, where the new signature panel outperformed markers published previously in terms of predicting biochemical recurrence. Our work also identified differences in gene expression between Gleason pattern 4 + 3 and 3 + 4 tumors, including several genes involved in the epithelial-to-mesenchymal transition and developmental pathways. Overall, this study defines a novel biomarker panel that has the potential to improve the clinical management of prostate cancer.
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Qi
Q
Long
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Jianpeng
J
Xu
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department o
Adeboye O
AO
Osunkoya
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Soma
S
Sannigrahi
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Brent A
BA
Johnson
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department o
Wei
W
Zhou
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Theresa
T
Gillespie
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Jong Y
JY
Park
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Robert K
RK
Nam
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Linda
L
Sugar
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Aleksandra
A
Stanimirovic
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
Arun K
AK
Seth
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department o
John A
JA
Petros
Authors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, OntarioAuthors' Affiliations: Departments of Biomedical Informatics, Biostatistics and Bioinformatics, Pathology and Laboratory Medicine, Urology, Hematology and Medical Oncology, Human Genetics, and Surgery; Winship Cancer Institute, Emory University, Atlanta; Atlanta VA Medical Center, Decatur, Georgia; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida; Department of Laboratory Medicine and Pathobiology, University of Toronto; and Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario cmoreno@emory.edu.
Carlos S
CS
Moreno
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005404:Fixatives / Q000737:chemistry; D005557:Formaldehyde / Q000737:chemistry; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017423:Sequence Analysis, RNA; D059467:Transcriptome
D014408:Biomarkers, Tumor; D005404:Fixatives; D005557:Formaldehyde