SOX2 & PDL1 Expression on Urinary Bladder Carcinoma

Urinary Bladder Neoplasm Clinical Trial

Official title:

Immunohistochemical Expression of SOX2 and PD-L1 as Valuable Prognostic Markers in Urinary Bladder Carcinoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05429710
• Other study ID #: Soh-med-22-06-13
• Status: Not yet recruiting
• Start date: October 1, 2022
• Est. completion date: December 1, 2023

Study information

• Verified date: June 2022
• Source: Sohag University
• Contact: alaa MS elmaghraby
• Phone: 01008723273
• Email: alaa.s.elmaghraby[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Bladder carcinoma (BC) is the 13th leading cause of cancer mortality worldwide . In Egypt, BC is the third common malignant tumor. Its incidence is 8.7% of all malignant tumors in both sexes with more predominance in males as reported by National Cancer Registry with more expected cases in the future.

There are different histological variants of BC which show different phenotypic, biological and prognostic impacts. The most common histological type of BC is urothelial carcinoma which constitutes about 90% of all bladder cancers. Squamous cell carcinoma, adenocarcinoma and other rare types represent the remaining 10%.

Carcinoma of the bladder is considered a heterogeneous stem cell tumor with increasing morbidity and death rates if it is not treated properly. The presence of cancer stem cells (CSCs) is associated with tumor progression, recurrence, metastasis, and resistance to conventional chemotherapy and makes complete elimination of the tumor difficult. Successes in treatment plans need more understanding of the CSCs population and their molecular biology.

The most important items of CSCs regulatory core are transcription factors such as OCT4, SOX-2, and Nanog. They play an important role in the regulatory network for maintaining the 'stemness' state of stem cells.

SOX2 (short for Sex determing Region Y - box 2), a High Mobility Group (HMG) domain transcription factor is member of the SRY-related HMG-box (SOX) family of transcription factors involved in the pluripotency, self-reappearance and differentiation of embryonic stem cell.

Cancer immunotherapy starts with a proper understanding of tumor immuno-biology. Study of the tumor microenvironment revealed the importance of immune checkpoints in facilitating tumor immunological escape, leading to the development of multiple novel therapeutics targeting the PD-1/PD-L1 (programmed cell death protein 1, "CD279" programmed death ligand 1, "CD274") immune checkpoints. And recently the expression levels of PD-L1 are closely associated with CSCs immune escape.

PD-1 is a T-cell immune inhibitory checkpoint that inhibit T-cell activation and contributes to the immunosuppressive tumor microenvironment. PD-1 is also expressed on activated B cells and natural killer cells. PD-1 is activated by binding to its ligand; PD-L1, which is a type I trans-membrane glycoprotein. Many cell types express PD-L1, including placenta, vascular endothelium, hepatocytes and mesenchymal stem cells, also B cells, T cells, dendritic cells, macrophages, and mast cells.

PD-L1 is considered to be a co-inhibitory factor of the immune response, it can combine with PD-1 to reduce the proliferation of PD-1 positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 also plays an important prognostic and predictive value in various malignancies where it can attenuate the host immune response to tumor cells.

However, little is known about the role of PD-L1 and its relation to SOX2 in urinary bladder carcinoma including its different histopathological variants. In this study, the main objective is to evaluate the immunohistochemical expression of PD-L1 to CSCs marker (SOX2) in urinary bladder carcinoma as a prognostic factor and search for new prospective targeted cancer therapy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 1, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patient with urinary bladder carcinoma.

• Specimen with submitted muscle layer

Exclusion Criteria:

• Patients with insufficient clinical data.

• Patients with recurrence of the primary tumor.

• Specimens with extensive necrosis

Related Conditions & MeSH terms

• Carcinoma
• Urinary Bladder Neoplasm
• Urinary Bladder Neoplasms

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sohag University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunohistochemical Expression of SOX2 and PD-L1 as valuable prognostic markers in Urinary Bladder Carcinoma	To evaluate the expression of SOX2 and PD-L1 in urinary bladder carcinomas	one or two days after staining sections with the markers