Genomic Imprinting Testing for Diagnosis of Bladder Cancer

Evaluation of Genomic Imprinting Testing for Detection and Surveillance of Bladder Cancer Patients

Urine analysis provide a promising non-invasive liquid biopsy for diagnosis of bladder cancer. Molecular biomarkers in urine may serve as important diagnostic and prognostic indicators for bladder cancer. Many alterations of genes and proteins have been identified in the urinary for diagnosis of bladder cancer. However, not all bladder cancer patients have the same alterations due to tumor heterogeneity. Thus, to reach satisfactory sensitivity and specificity a new diagnostic molecular alteration should exists ubiquitously in cancers. Numerous studies indicate that Loss of imprinting (LOI) exists ubiquitously in cancers and precede morphological changes. The investigators will conduct a prospective evaluation of a panel of LOI changes in urine test for detection and surveillance of bladder cancer patients.

Study Overview

• Status: Unknown
• Conditions: Bladder Cancer; Diagnoses Disease; Urine Marking
• Intervention / Treatment: Diagnostic test: Genomic Imprinting Testing

Detailed Description

During the progression of tumor, molecular changes in both genomics and epigenomics occur prior to morphological changes in cells and tissues, therefore molecular biological test is more sensitive to detect cancer at early stage. Genomic imprinting is one kind of epigenetic regulation that controls gene expression. In detail, a copy of gene on the certain maternal or paternal allele is silenced through methylation, while the other acts normally. This kind of genes are named imprinting genes. Loss of imprinting and Copy number variation (LOI & CNV) is epigenetic change that the silenced copy of an imprinting gene is activated through demethylation. Numerous studies indicate that LOI exists ubiquitously in cancers and precede morphological changes. In contrast, LOI rarely happens in normal somatic cells. Therefore, the methylation status of imprinting genes can act as a biomarker to detect and analyze the abnormal cells.

The investigators will develop a couple of common LOI to establish a predictive diagnostic LOI panel in urine with optimal and robust efficacy in diagnosis of bladder cancer by analyzing LOI in urine from bladder cancer patients and control group that without any tumor in urinary system or other organs. Moreover, the changes of LOI in urine collected before and 1 year after transurethral resection of non-muscle invasive bladder cancer (NIMBC) will also be monitored. External consistency validation will be performed on subsequent urine from patients and control participants collection.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Changhai Hospital
      • Contact: Chuanliang Xu, M.D., Ph.D; Phone Number: +86 18930568759; Email: drxuchuanliang@126.com
      • Contact: Yinghao Sun, M.D., Ph.D; Email: sunyhsmmu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with bladder cancer or participants in control group in Changhai Hospital from December 2017 till the end of this study.

Description

Inclusion Criteria:

- 1. Patients diagnosed with of bladder cancer by cystoscopy and biopsy. 2. Participants without any tumor disease and willing to attend the study by providing morning urine.

3. Moring urine and available tumor tissue obtained by biopsy. 4. Male or female patients aged >= 18 years. 5. Participants signed informed consent form.

Exclusion Criteria:

- 1. Age under 18 years 2. Individuals unwilling to sign the IRB-approved consent form and unwilling to follow the protocol to submit the serial urine for test after surgery 3. Comorbidities that will prohibit or make serial urine collection and cystoscopic examination difficult or impossible during follow up.

4. Prior diagnosis of cancer except bladder cancer

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bladder cancer patients; Diagnosed bladder cancer patients who are being monitored will be the experimental group to develop the LOI panel, and subsequent cohort will be used to confirm the sensitivity and specificity of this urinary analysis.	Diagnostic test: Genomic Imprinting Testing; The changes of LOI The obtained LOI from morning urine and tumor will be tested by LiSen imprinting diagnostic (LSID)
Non-cancer participants; Patients being treated for other diseases but without any tumor or healthy participants will provide a negative control to provide data for developing the LOI diagnostic panel	Diagnostic test: Genomic Imprinting Testing; The changes of LOI The obtained LOI from morning urine and tumor will be tested by LiSen imprinting diagnostic (LSID)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of urinalysis by LOI urine analysis	Number of patients "declared positive" with the LOI urine test among the patients suffered from bladder cancer	In the middle of the study, an average of 12 months
Specificity of urinalysis by LOI urine analysis	Number of patients "declared negative" with the LOI urine test among the patients who are without cancer	In the middle of the study, an average of 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of sensitivity of urinalysis by LOI urine analysis to predict the recurrence of bladder cancer within 1 year after transurethral resection of NMIBC	Number of patients "declared positive" with the LOI urine test after bladder cancer surgery among the patients being confirmed to have bladder cancer by cystoscopic examination and biopsy	Through study completion, an average of 24 months
Identification of specificity of urinalysis by LOI urine analysis to predict the free of bladder cancer recurrence within 1 year after transurethral resection of NMIBC	Number of patients "declared negative" with the LOI urine test after bladder cancer surgery among the patients being confirmed to have no bladder cancer recurrence by cystoscopic examination	Through study completion, an average of 24 months
Comparison of the sensitivity of the urine LOI analysis versus urine cytology	Number of patients "declared positive" with the LOI analysis versus patients "declared positive" with the urine cytology	In the middle of the study, an average of 12 months
Comparison of the specificity of the urine LOI analysis versus urine cytology	Number of patients "declared negative" with the LOI analysis versus patients " declared negative " with the urine cytology	In the middle of the study, an average of 12 months

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: LiSen imprinting diagnostic (LSID) Company
• Investigators: Principal Investigator: Chuangliang Xu, M.D., Ph.D, Changhai Hospital

Publications and helpful links

General Publications

• Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol. 2007 Feb;211(3):261-8. doi: 10.1002/path.2116.
• Haig D. Maternal-fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer. Philos Trans R Soc Lond B Biol Sci. 2015 Jul 19;370(1673):20140178. doi: 10.1098/rstb.2014.0178.
• Uribe-Lewis S, Woodfine K, Stojic L, Murrell A. Molecular mechanisms of genomic imprinting and clinical implications for cancer. Expert Rev Mol Med. 2011 Jan 25;13:e2. doi: 10.1017/S1462399410001717.
• Jirtle RL. Genomic imprinting and cancer. Exp Cell Res. 1999 Apr 10;248(1):18-24. doi: 10.1006/excr.1999.4453.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 15, 2017
• Primary Completion (ANTICIPATED): December 15, 2018
• Study Completion (ANTICIPATED): December 15, 2019

Study Registration Dates

• First Submitted: June 10, 2018
• First Submitted That Met QC Criteria: June 10, 2018
• First Posted (ACTUAL): June 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 10, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Diagnosis; Bladder Cancer; Surveillance; Urine biomarker; Genomic imprinting
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Disease; Urinary Bladder Neoplasms
• Other Study ID Numbers: CH-urology-bladder marker-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No