Development of a Non-Invasive DNA Methylation-Based Assay System for the Risk Assessment of Urothelial Carcinoma

Bladder cancer ranks the ninth in worldwide cancer incidence. Approximate 90% of bladder cancer is the malignancy of urothelium tissues, the urothelial cancer (UC). The mortality of bladder cancer is mainly due to recurrence and metastasis. Unfortunately, the currently available cytology or cystoscopy examination is of limited value because of low sensitivity of early disease. New biomarkers as well as detection technology are thus required to improve early diagnosis. By the aid of quantitative methylation-specific PCR (QMSP), which allows detecting tumor-derived DNA from tissues and body fluids, DNA methylation-based assay is thus developing for early detection and prognosis.

The goal of this proposed project is to develop a panel of DNA-methylation based biomarkers for UC diagnosis, prognosis, and prediction of responses to therapy (especially the recurrence, invasion, survival, and responses to therapeutic agents). Although numerous studies have investigated the aberrant promoter hypermethylation in bladder cancers or UC, inconsistent results are observed. DNA hypermethylation determination may rely on not only the conditions of QMSP, but also the biopsy specimens of different race, environmental expose factors, and regional variation. We thus need to profile the DNA methylation pattern of UC patients in Taiwan to establish a panel of potential prediction biomarkers for local patients.

Study Overview

• Status: Unknown
• Conditions: Bladder Cancer

Detailed Description

In the recent years, technologies of genomics, expression analysis and proteomics have been brought to guide the study of risk assessment and early detection of cancers. This proposed study aims to develop a non-invasive DNA methylation-based assay system elucidating a panel of aberrantly hypermethylated genes from urothelial tumors and urine sediments, to improve the risk assessment of urothelial carcinoma; such as early diagnosis, prognosis, and prediction of response to therapeutic regimes. This proposal will establish several techniques to study the methylation status on gene promoter regions. Three tasks will be achieved in this study: (1) Profiling the aberrant DNA methylation in urothelial carcinoma and determining potential prediction biomarkers. (2) Establishing a non-invasive assay by detecting DNA hypermethylation status in exfoliated cells collected from void urine; (3) Mapping the DNA hypermethylation changes from normal to malignant urothelial tumors and studying the underlying mechanism. Through the collaboration of a genetic toxicologist (Te-Chang Lee, PhD, IBMS), a urologist (Yeong-Shiau Pu, MD/PhD, NTUH) and epidemiologists (Hung-Yi Chiou, PhD, Taipei Medical University), we will explore the risk biomarkers for urothelial carcinoma.

• Study Type: Observational
• Enrollment (Anticipated): 82

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study subjects from the Department of Urology of NTUH. Those with urothelial carcinoma(bladder, renal pelvis and ureter) will be recruited in this study period. After they signed the informed consent,we will ask them some questions through face-to-face interview and collect 6-8ml blood and 50c.c. urine. Then genomic DNA will be extracted from these biospecimens to perform a non-invasive DNA methylation-based assay.

Description

Inclusion Criteria:

• those with histopathological-confirmed urothelial carcinoma will be included.

Exclusion Criteria:

• those were younger than 40 years old or with previous history of any other cancers will be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; case group: patients with urothelial carcinoma
2; control group: those without previous history of any malignancy

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: HUNG-YI CHIOU, PhD, COLLEGE OF PUBLIC HEALTH, TAIPEI MEDICAL UNIVERSITY; Principal Investigator: Yeong-Shiau Pu, MD, Department of Urology, National Taiwan University Hospital; Principal Investigator: Te-Chang Lee, PhD, Institute of Biomedical Sciences, Academia Sinica

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Study Completion (Anticipated): July 1, 2010

Study Registration Dates

• First Submitted: March 22, 2009
• First Submitted That Met QC Criteria: March 22, 2009
• First Posted (Estimate): March 24, 2009

Study Record Updates

• Last Update Posted (Estimate): March 24, 2009
• Last Update Submitted That Met QC Criteria: March 22, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Transitional Cell
• Other Study ID Numbers: 200707055R