Clinical trial NCT03563443: Genomic Imprinting Testing for Diagnosis of Bladder Cancer
Official title: Evaluation of Genomic Imprinting Testing for Detection and Surveillance of Bladder Cancer Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bladder Cancer
Urine Marking
Diagnoses Disease
Keywords: Bladder Cancer
Genomic imprinting
Urine biomarker
Diagnosis
Surveillance
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
Collaborators: name: LiSen imprinting diagnostic (LSID) Company
First posted: 2018-06-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity of urinalysis by LOI urine analysis
timeFrame: In the middle of the study, an average of 12 months
measure: Specificity of urinalysis by LOI urine analysis
timeFrame: In the middle of the study, an average of 12 months
Secondary outcomes:
measure: Identification of sensitivity of urinalysis by LOI urine analysis to predict the recurrence of bladder cancer within 1 year after transurethral resection of NMIBC
timeFrame: Through study completion, an average of 24 months
measure: 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
timeFrame: Through study completion, an average of 24 months
measure: Comparison of the sensitivity of the urine LOI analysis versus urine cytology
timeFrame: In the middle of the study, an average of 12 months
measure: Comparison of the specificity of the urine LOI analysis versus urine cytology
timeFrame: In the middle of the study, an average of 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Changhai Hospital
name: Chuangliang Xu, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol. 2007 Feb;211(3):261-8. doi: 10.1002/path.2116.
citation: 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.
citation: 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.
citation: Jirtle RL. Genomic imprinting and cancer. Exp Cell Res. 1999 Apr 10;248(1):18-24. doi: 10.1006/excr.1999.4453.