SOX2 & PDL1 Expression on Urinary Bladder Carcinoma

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Urinary Bladder Neoplasm

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: alaa MS elmaghraby; Phone Number: 01008723273; Email: alaa.s.elmaghraby@gmail.com
• Study Contact Backup: Name: alaa MS elmaghraby; Phone Number: 01285230523; Email: alaa.elmaghraby@med.sohag.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Formaline fixed and paraffine embedded urinary bladder tissue block from 60 patient

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Sohag University
• Investigators: Principal Investigator: alaa MS elmaghraby, Sohag University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: SOX2, PDL1, prgnosis, urinary bladder carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Carcinoma; Urinary Bladder Neoplasms
• Other Study ID Numbers: Soh-med-22-06-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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