MP28-20 EXPRESSION OF HMGB1 IN PROSTATE CANCER: CLINICAL AND BIOLOGICAL CORRELATIONS

Abstract

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2017MP28-20 EXPRESSION OF HMGB1 IN PROSTATE CANCER: CLINICAL AND BIOLOGICAL CORRELATIONS Yong Hyun Park, Ae Ryang Jung, Jin Bong Choi, U-Syn Ha, Sung-Hoo Hong, Sae Woong Kim, and Ji Youl Lee Yong Hyun ParkYong Hyun Park More articles by this author , Ae Ryang JungAe Ryang Jung More articles by this author , Jin Bong ChoiJin Bong Choi More articles by this author , U-Syn HaU-Syn Ha More articles by this author , Sung-Hoo HongSung-Hoo Hong More articles by this author , Sae Woong KimSae Woong Kim More articles by this author , and Ji Youl LeeJi Youl Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.833AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The high mobility group box1 (HMGB1), which is the important nuclear factor, has been noted to play a critical role of biological processes such as DNA repair, transcription and extracellular response. Increased expression of HMGB1 has been observed in several solid cancers and known to be associated with poor prognosis. However, there have been little studies of the role of HMGB1 in prostate cancer (PCa) development and progression. Therefore, in this study, we aimed to investigate 1) the role of HMGB1 on cellular proliferation, apoptosis, migration, and invasion, 2) the underlying biological mechanisms of HMGB1 in PCa, and 3) the expression pattern of HMGB1 in PCa patients with different stage and grade and its prognostic importance. METHODS After transient transfection of PC3 and DU-145 cells with HMGB1 siRNA, diverse experiments were performed to evaluate the changes in proliferation, apoptosis, migration and invasion. To determine whether HMGB1 affects the NF-?B pathway, subcellular localizations of p65 and phosphorylated p65 were assessed by western blot analysis. Using the Cancer Genome Atlas (TCGA) datasets, we determined the impact of HMGB1 on overall survival in PCa. We further validated the prognostic importance of HMGB1 by immunofluorescence staining in 131 PCa patients from the Korean Prostate Bank. RESULTS Inhibition of HMGB1 expression significantly reduced cell proliferation and increased cell cycle arrest in the sub-Go phase of PC3 and DU-145 cells. It also inhibited the migration and invasive capacity of PCa cells. Western blot analysis showed that inhibition of HMGB1 reduced p65 and phosphorylated p65 protein levels in nuclear fractions of PCa cells. In The Cancer Genome Atlas data set (n = 498), HMGB1 was altered in 61 of 498 patients (12%). Overall survival was shorter in the high HMGB1 expression group (medians: 115.0 months vs. not reached; P = 0.0296). In the Korean Prostate Bank cohort, the positive areas of HMGB1 differed in patients with BPH, and low-, intermediate-, high-risk, and metastatic PCa (4.6, 11.9, 18.6, 19.7, and 23.4%, p < 0.001). During the median follow-up of 32 months, increased expression of HMGB1 was associated with a significant decrease in biochemical recurrence free survival on Kaplan-Meier analysis. CONCLUSIONS Our findings demonstrate an important role of HMGB1 and novel relationship between HMGB1 and NF-?B pathway in PCa. Therapy targeting HMGB-associated pathways may represent a novel therapeutic avenue for PCa. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e346 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Yong Hyun Park More articles by this author Ae Ryang Jung More articles by this author Jin Bong Choi More articles by this author U-Syn Ha More articles by this author Sung-Hoo Hong More articles by this author Sae Woong Kim More articles by this author Ji Youl Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...