Smurf2 Gene Expression in Urinary Tract Tumors

Smurf2 Gene Expression in Urinary Tract Tumors - Tissue Immunohistochemitry and Urinary Sediment Analysis

Smurf2 and bladder cancer - research proposal summary The Smurf2 gene was recently identified as a tumor suppressor gene. It is an E3 ubiquitin ligase and carries a significant role in major cellular processes such as cell division, genomic stability, DNA repair as well as resistance to anti-tumoral drugs.

Recent studies showed that in several common tumors (prostate, breast, osteosarcoma etc.), a significant decrease in the expression or activity of Smurf2 can be noted, making the cells more susceptible to malignant transformation and the tumors more aggressive and highly resistant to various medications.

Bladder cancer is no. 4 cancer in men and 6 in women, and a major cause of cancer related death. Common risk factors are smoking and occupational exposure to aniline dyes or aromatic amines. Its' most common presentation is painless hematuria. Once the diagnosis of a bladder tumor is made, endoscopic resection of the tumors is performed. Superficial tumors of low malignancy may be treated by repeated resections, highly malignant tumors require additional therapy and aggressive tumors invading the bladder muscle layer require radical surgery and chemo-radiotherapy. Therefore, all patients are closely monitored by repeated cystoscopies (endoscopic inspection of the bladder), each 3 months, lifelong.

In an effort to minimize patients' discomfort, there is a constant search for a reliable biomarker in the urine of patients. A marker with good sensitivity and specificity will predict in a noninvasive fashion early recurrence or absence of bladder tumors, sparing the need for invasive cystoscopy. The presence of a biomarker may be used as prognostic factor or a measure of response to therapy.

The aim of this research is to characterize the presence of smurf2 in bladder tumors and determine whether it may be utilized as a reliable biomarker for bladder cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Neoplasm
• Intervention / Treatment: Diagnostic test: immunohistochemistry of tumors samples

Detailed Description

Smurf2 and bladder cancer - research proposal summary - detailed

The Smurf2 gene was recently identified as a tumor suppressor gene. It is an E3 ubiquitin ligase and carries a significant role in major cellular processes such as cell division, genomic stability, DNA repair as well as resistance to anti-tumoral drugs.

Recent studies showed that in several common tumors (prostate, breast, osteosarcoma etc.), a significant decrease in the expression or activity of Smurf2 can be noted, making the cells more susceptible to malignant transformation and the tumors more aggressive and highly resistant to various medications.

Bladder cancer is no. 4 cancer in men and 6 in women, and a major cause of cancer related death. Common risk factors are cigarrete smoking and occupational exposure to aniline dyes or aromatic amines. Its' most common presentation is painless hematuria. Once the diagnosis of a bladder tumor is made, endoscopic resection of the tumors is performed. Superficial tumors of low malignancy may be treated by repeated resections, highly malignant tumors require additional therapy and aggressive tumors invading the bladder muscle layer require radical surgery and chemo-radiotherapy. Therefore, all patients are closely monitored by repeated cystoscopies (endoscopic inspection of the bladder.

In an effort to minimize patients' discomfort, there is a constant search for a reliable biomarker in the urine of patients. A marker with good sensitivity and specificity will predict in a noninvasive fashion early recurrence or absence of bladder tumors, sparing the need for invasive cystoscopy. The presence of a biomarker may be used as prognostic factor or a measure of response to therapy.

The aim of this research is to characterize the presence of smurf2 in bladder tumors and determine whether it may be utilized as a reliable biomarker for bladder cancer.

In the study, the investigators will collect samples from bladder tumors of patient referred for transurethral resection of a known bladder tumor. The tissue will be processed routinely yet additional slides will be performed and used for immunohistochemical analysis. The investigators will characterize the expression of SMURF2 in the tissue, its abundance, the distribution between the nucleus and cytoplasm and possible differences between the tumors tissue and surrounding normal margins.

Further on, the investigators will collect urine samples from patients with these tumors and examine the urinary sediment using PCR and proteomic examination. The data will be used for further research using the SMURF2 product as a possible novel bio-marker for the presence of bladder tumors and for non-invasive detection and follow-up of patients on surveillance following surgical treatment.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Ran Katz, MD; Phone Number: +972-4-6828775; Email: rank@ziv.gov.il
• Study Contact Backup: Name: Hiba Khuri, MSc; Phone Number: +972-52-5100979; Email: hibak@ziv.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Male patients, diagnosed with bladder tumors, referred for transurethral resection

Description

Inclusion Criteria:

• Identified bladder tumor
• Scheduled for transurethral resection
• Informed consent

Exclusion Criteria:

• Previous bladder, prostate or pelvic irradiation
• Persistent urinary tract infection
• Intravesical therpy with BCG within 6 months prior to surgery.
• Intravesical chemotherapy within 6 months prior to surgery

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smurf2 and bladder cancer	The presence of SMURF2 in bladder tumor tissue compared to normal surrounding tissue	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smurf2 and bladder cancer	The distribution of SMURF2 in bladder tumor cells - nucleus to cytoplasm	6 months
Smurf2 and bladder cancer	Identification of the SMURF2 product in the urinary sediment using proteomics and PCR	6 months

Collaborators and Investigators

• Sponsor: Ziv Hospital
• Collaborators: Azrieli Faculty of medicine, Bar Ilan University, Safed, IL
• Investigators: Study Director: Ran Katz, MD, Ziv Medical Center

Publications and helpful links

General Publications

• Manikoth Ayyathan D, Koganti P, Marcu-Malina V, Litmanovitch T, Trakhtenbrot L, Emanuelli A, Apel-Sarid L, Blank M. SMURF2 prevents detrimental changes to chromatin, protecting human dermal fibroblasts from chromosomal instability and tumorigenesis. Oncogene. 2020 Apr;39(16):3396-3410. doi: 10.1038/s41388-020-1226-3. Epub 2020 Feb 26.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: November 14, 2021
• First Submitted That Met QC Criteria: November 14, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): December 16, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: biomarker; PCR; immunohistochemistry; bllader neoplasm,; SMURF2; urinary sediment
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Urologic Neoplasms
• Other Study ID Numbers: 0029-20-ZIV

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