PD65-03 IDENTIFICATION OF PROGNOSTIC GENES THAT DETERMINE MRI VISIBILITY

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology IV1 Apr 2018PD65-03 IDENTIFICATION OF PROGNOSTIC GENES THAT DETERMINE MRI VISIBILITY Ping Li PhD, Sungyong You PhD, Hanson H Zhao MD, Christopher Nguyen PhD, Yanping Wang MD, Jayoung Kim PhD, Deepika Sirohi MD, Asha Ziembiec MD, Daniel Luthringer MD, Shih-Chieh Lin PhD, Timothy Daskivich MD, Jonathan Wu MD, Michael R Freeman PhD, Rola Saouaf MD, Debiao Li PhD, and Hyung L Kim MD Ping Li PhDPing Li PhD More articles by this author , Sungyong You PhDSungyong You PhD More articles by this author , Hanson H Zhao MDHanson H Zhao MD More articles by this author , Christopher Nguyen PhDChristopher Nguyen PhD More articles by this author , Yanping Wang MDYanping Wang MD More articles by this author , Jayoung Kim PhDJayoung Kim PhD More articles by this author , Deepika Sirohi MDDeepika Sirohi MD More articles by this author , Asha Ziembiec MDAsha Ziembiec MD More articles by this author , Daniel Luthringer MDDaniel Luthringer MD More articles by this author , Shih-Chieh Lin PhDShih-Chieh Lin PhD More articles by this author , Timothy Daskivich MDTimothy Daskivich MD More articles by this author , Jonathan Wu MDJonathan Wu MD More articles by this author , Michael R Freeman PhDMichael R Freeman PhD More articles by this author , Rola Saouaf MDRola Saouaf MD More articles by this author , Debiao Li PhDDebiao Li PhD More articles by this author , and Hyung L Kim MDHyung L Kim MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2987AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Multiparametric magnetic resonance imaging (MRI) is widely used to aid the diagnosis and treatment of prostate cancer. However, not all tumors are seen on MRI, including some high grade and potentially lethal tumors. We aim to better understand the molecular basis and prognostic implications for tumor visibility on MRI. METHODS Detailed maps of prostate cancers were created using radical prostatectomy specimens. Tumors visible and invisible on MRI were macrodissected and analyzed by RNA sequencing. Differentially expressed genes (DEGs) were cross-referenced with public databases to identify genes associated with disease progression, metastasis and MRI visibility. A multivariate analysis was performed using these genes along with standard clinical variables. One of these genes was knocked-down in a human prostate cancer cell line. This was used to generate xenograft tumors in mice that were imaged on MRI. RESULTS 1,654 DEGs were identified based on MRI visibility status. DEGs based on Gleason score and tumor size were also identified. Gleason score (dissimilarity test, p<0.0001) and tumor size (p<0.039) did not fully explain MRI visibility. Four genes (PHYDH1, CENPF, ALDH2, GDF15) predicted MRI visibility, were associated with metastasis, and predicted progression free survival. These fours genes (MRI4) did not correlate with tumor size (r=-0.62 to 0.41) suggesting that MRI4 does not simply reflect tumor growth. Multivariate analysis showed that MRI4 was a significant predictor of recurrence free survival independent of PSA, stage, and grade (p=0.021). A reciprocal analysis of genes in two previously published prognostic signatures also predicted MRI visibility in our dataset. A human prostate cancer cell line was engineered to express MicroRNA-101 in the presence of doxycycline, which negatively regulates CENPF. The resulting tumors injected in mice fed doxycycline had decreased tumor growth and visibility on MRI. Immunohistochemical analysis suggests that decreased MRI visibility in these mice was due to decreased cell density and proliferation. CONCLUSIONS MRI visibility suggests a more favorable prognosis in prostate cancer. We identified four prognostic genes associated with MRI visibility, progression free survival, and metastasis. In animal studies, genetic manipulation of CENPF resulted in altered MRI visibility. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1225 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ping Li PhD More articles by this author Sungyong You PhD More articles by this author Hanson H Zhao MD More articles by this author Christopher Nguyen PhD More articles by this author Yanping Wang MD More articles by this author Jayoung Kim PhD More articles by this author Deepika Sirohi MD More articles by this author Asha Ziembiec MD More articles by this author Daniel Luthringer MD More articles by this author Shih-Chieh Lin PhD More articles by this author Timothy Daskivich MD More articles by this author Jonathan Wu MD More articles by this author Michael R Freeman PhD More articles by this author Rola Saouaf MD More articles by this author Debiao Li PhD More articles by this author Hyung L Kim MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...