DNA Methylation of GSTP1 in Human Prostate Tissues: Pyrosequencing Analysis

윤형윤,김영원,강호원,김원태,윤석중,이상철,김원재,김용준 대한비뇨의학회 2012 Investigative and Clinical Urology Vol.53 No.3

Purpose: DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumor initiation and progression. Differences in methylation patterns between neoplastic and normal cells can be used to detect the presence of cancer. The aim of the present study was to evaluate the usefulness of glutathione-S-transferase-Pi (GSTP1) hypermethylation in discriminating between normal and prostate cancer (PCa) cells and in predicting tumor characteristics by use of quantitative pyrosequencing analysis. Materials and Methods: A total of 100 human prostate tissues obtained from our institute were used in this study: 45 for benign prostatic hyperplasia (BPH) and 55 for PCa. The methylation level of GSTP1 was examined by a quantitative pyrosequencing analysis. The associations between GSTP1 methylation level and clinico-pathological parameter were also compared. Results: The level of GSTP1 methylation was significantly higher in PCa samples than in BPH samples (56.7±32.7% vs. 1.6±2.2%, p<0.001). The sensitivity and specificity of GSTP1 methylation status in discriminating between PCa and BPH reached 85.5% and 100%, respectively. Even after stratification by stage, Gleason score, and prostate-specific antigen (PSA) level, similar results were obtained. A positive correlation between GSTP1 methylation level and serum PSA level was observed (r=0.303, p=0.002). There were no associations between GSTP1 methylation level and age, Gleason score, and staging. Conclusions: Our study demonstrates that GSTP1 methylation is associated with the presence of PCa and PSA levels. This methylation marker is a potentially useful indicator for the detection and monitoring of PCa.

Pyrosequencing Analysis of APC Methylation Level in Human Prostate Tissues: A Molecular Marker for Prostate Cancer

윤형윤,김영원,강호원,김원태,윤석중,이상철,김원재,김용준 대한비뇨의학회 2013 Investigative and Clinical Urology Vol.54 No.3

Purpose: Epigenetic alterations such as abnormal DNA methylation are associated with many human cancers. Differences in methylation patterns between neoplastic and normal cells can be used to detect cancer. The aim of the present study was to evaluate the effectiveness of detecting Adenomatous polyposis coli (APC) hypermethylation by quantitative pyrosequencing for discriminating between normal and prostate cancer (PCa) cells and for predicting tumor behaviors. Materials and Methods: A total of 218 human prostate tissues obtained from our institute were assessed: 106 specimens of benign prostatic hyperplasia (BPH) and 112specimens of PCa. The methylation status of APC was analyzed by quantitative pyrosequencing. The association between the APC methylation level and clinicopathological parameters was explored. Results: The level of APC methylation was significantly higher in PCa specimens than in BPH specimens (33.3%±20.7% vs. 1.3%±1.8%, p<0.001). The sensitivity and specificity of APC methylation status in discriminating between PCa and BPH reached 89.3%and 98.1%, respectively. Similar results were obtained after stratification by stage,Gleason score, and prostate-specific antigen level. The APC methylation level correlated positively with Gleason score (p trend=0.016). There was no association between the APC methylation level and the PSA level or staging. Conclusions: Our results demonstrate that APC methylation is associated with PCa and its aggressive tumor features.

T1b 병기의 신세포암에서 수술 후 예후를 예측할 수 있는 임상 및 병리학적 인자에 대한 연구

오승용, 김영원, 윤형윤, 서성필, 이상근, 김원태, 윤석중, 이상철, 김원재, 김용준 충북대학교 의과대학 충북대학교 의학연구소 2014 忠北醫大學術誌 Vol.24 No.1

연구목적: T1병기의 국소신세포암(localized clear-cell renal cell carcinoma)은 근치적신적출술이 나 부분신절제술이 표준치료이며 수술 후 타 병기에 비해 양호한 예후를 보인다. 하지만, 많은 수의 환 자에서 추적관찰 중 재발 및 사망이 발생하는데, 이는 T1b 병기에서 더 높게 보고되고 있다. 본 연구 에서는 국소신세포암 중 T1b 병기의 신세포암에서 표준적 치료 후 환자의 예후에 영향을 주는 임상 및 병리학적 인자에 대하여 알아보고자 하였다. 대상 및 방법: 1999년부터 2011년 까지 5개 기관에서 근치적신적출술이나 부분신제술을 시행 받은 3567명의 국소신세포암 환자들 중 병리학적 병기가 T1b로 확진 된 702명을 대상으로 하였다. 이들 환자가 가지는 임상 및 병리학적 특성 [연령, 성별, 고혈압, 당뇨, 비만도, European Cooperative Oncology Group(ECOG) 수행도, 증상유무, 수술방법, 종양크기, 분화도, 조직학적 형태 등]을 이용 하여 환자의 예후 [무재발생존율(relapse-free survival), 암특이생존율(cancer-specific survival) 및 전체생존율(overall survival)]에 영향을 미치는 인자에 대하여 다양한 방법으로 비교분석 하였다. 결과: 추적 관찰 기간은 34.0개월 (중앙값, 0-152개월)이었으며, 이 기간 중 재발, 사망 및 암특이사 망은 각각 72례 (10.3%), 57례 (8.1%) 및 24례 (3.4%)에서 발생하였다. 단변량 및 다변량 Cox 비례위험회귀분석에서 다양한 인자들이 무재발생존율(당뇨 유무, 종양크기 및 Fuhrman등급), 암특이 생존율(나이, 체질량지수, 당뇨 유무, 종양크기) 및 전체생존율(나이, 체질량지수, ECOG 수행도, 종 양크기)에 영향을 줄 수 있는 독립적 예후인자였다. 결론: 본 연구결과 국소신세포암의 예후를 예측할 수 있는 다양한 임상 및 병리학적 인자를 확인 할 수 있었다. 이러한 위험인자를 가지고 있는 환자는 보다 적극적인 추적관찰을 통하여 재발을 조기에 발 견한다면 이들의 생존율 향상에 많은 기여를 할 수 있을 것으로 생각한다.

FAM70B as a Novel Prognostic Marker for Cancer Progression and Cancer-Specific Death in Muscle-Invasive Bladder Cancer

강호원,윤형윤,하윤석,김원태,김용준,윤석중,이상철,김원재 대한비뇨의학회 2012 Investigative and Clinical Urology Vol.53 No.9

Purpose: To validate whether FAM70B, which was found in our micro-array profiling as a prognostic marker for cancer survival, could accurately predict prognosis in patients with muscle-invasive bladder cancer (MIBC). Materials and Methods: A total of 124 patients with MIBC were enrolled in this study. The FAM70B expression level was analyzed by real-time polymerase chain reaction by using RNA from tumor tissues. The prognostic effect of FAM70B was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. Results: Kaplan-Meier estimates showed a significant difference in progression-free survival (log-rank test, p=0.011) and cancer-specific survival (log-rank test, p=0.017) according to FAM70B gene expression level. By multivariate Cox regression analysis, high FAM70B expression was predictive of cancer progression (hazard ratio [HR], 2.115, p=0.013) and cancer-specific death (HR, 1.925; p=0.033). In the subgroup analysis, high expression of FAM70B was associated with poor cancer-specific survival, progression-free survival, and overall survival in the patients who underwent cystectomy (log-rank test, p=0.013, p=0.036, p=0.005, respectively). In the chemotherapy group, FAM70B expression was associated with cancer-specific survival and progression-free survival (log-rank test, p=0.013, p=0.042, respectively). Moreover, high FAM70B expression was associated with shorter cancer-specific survival in localized or locally advanced tumor stages (log-rank test, p=0.016). Conclusions: We confirmed the significance of FAM70B as a prognostic marker in a validation cohort. Therefore, we propose that the FAM70B gene could be used to more precisely predict cancer progression and cancer-specific death in patients with MIBC.

mRNA Expression of S100A8 as a Prognostic Marker for Progression of Non-Muscle-Invasive Bladder Cancer

하윤석,김민주,윤형윤,강호원,김용준,윤석중,이상철,김원재 대한비뇨의학회 2010 Investigative and Clinical Urology Vol.51 No.1

Purpose: S100A8 is a member of the S100 protein family containing 2EF-hand calcium-binding motifs. S100 proteins are involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. Altered expression of this protein is associated with various diseases and cancers. The present study aimed to evaluate whether S100A8 has prognostic value for non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: A total of 103 primary NMIBC samples obtained by transurethral resection were evaluated. mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results were compared with clinico-pathological parameters. The Kaplan-Meier method was applied to plot the curves for progression-free survival. The multivariate Cox regression model was used to identify the independent prognostic factors for progression. Results: mRNA expression levels of S100A8 were significantly related to the progression of NMIBC. Kaplan-Meier estimates demonstrated significant differences in tumor progression according to the level of S100A8 expression (log-rank test, p<0.001). The multivariate Cox regression model revealed that the S100A8 mRNA expression level (hazard ratio: 12.538; 95% confidence interval: 2.245-70.023, p=0.004) was an independent predictor for disease progression of NMIBC. Conclusions: Expression levels of S100A8 might be a useful prognostic marker for disease progression of NMIBC.

Lower Levels of Human MOB3B Are Associated with Prostate Cancer Susceptibility and Aggressive Clinicopathological Characteristics

김은아,김예환,강호원,윤형윤,김원태,김용준,윤석중,문성권,최영현,Isaac Yi Kim,이상철,김원재 대한의학회 2015 Journal of Korean medical science Vol.30 No.7

Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P < 0.001). According to receiver operating characteristics curve analysis, the sensitivity of hMOB3B expression for PCa diagnosis was 84.7%, with a specificity of 86% (AUC = 0.910; 95% CI = 0.869- 0.941; P < 0.001). hMOB3B expression was significantly lower in patients with elevated prostate specific antigen (PSA) levels (≥ 10 ng/mL), a Gleason score ≥ 8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and nonmetastatic disease (each P < 0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa.

아버지의 자녀양육 행동에 관한 실태 조사

문정언,김희정,노혜연,윤형윤,이명선,전경아 연세대학교 생활과학대학 1995 婦學 Vol.28 No.-