The Role of Programmed Death Ligand -1 (Pdl-1) in Lung Cancer

Lung Cancer Clinical Trial

Official title:

The Role of Programmed Death Ligand -1 (Pdl-1) in Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05082636
• Other study ID #: PDL-1 Lung Cancer
• Status: Completed
• Start date: June 15, 2018
• Est. completion date: March 25, 2021

Study information

• Verified date: October 2021
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This study was designed to investigate the correlation of lung cancer tissue expression of both PDL-1-mRNA ,vitamin D receptor (VDR) and level of vit.D in sera of lung cancer patients.These three biochemical markers may interact and play a role in lung cancer progression.

Description:

Lung cancer is the leading cause of cancer death worldwide. In 2018, it represented 11.6% of total cancer cases and 18.4% of total cancer deaths, making it the most frequent cancer and cause of cancer death in men and women combined .In Egypt, Lung cancer represents the most lethal malignancy and the fourth most common cancer in men.It is relatively more common in men. This gender difference in incidence is mainly due to differences in tobacco smoking rates, as smoking represents the major risk factor of this disease.

Programmed cell death 1 (PD-1) (Entrez Gene: 29126) and its ligand, programmed cell death ligand-1 (PDL-1) are new members of the CD28/B7 stimulatory superfamily. They mediate a negative signal, which inhibits functioning and proliferation of T and B cells, and reduce interleukin-2(IL-2), IL-10, and interferon-γ secretions.This inhibitory pathway is closely related to tumor progression, it provides an immune escape for tumor cells through cytotoxic T-cell inactivation. It plays an important role in the microenvironment of the tumor progress.Expression of this gene in tumor cells is prognostic in many types of human malignancies.Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response with local immune tolerance to tumors.

The biologically active form of Vit D, namely calcitriol or 1,25-dihydroxy Vitamin D (1,25(OH)2D ), is generated when 25(OH)D is hydroxylated in the kidneys by the cytochrome 1-α- hydroxylase enzyme (CYP27B1) (RXR) Yet, Vit. D has controversial effects; it has been shown to induce apoptosis of cancer cells and likely to play a promising role in cancer therapy.Numerous studies have proposed a strong relationship between low serum Vit. D levels and increased risk of cancer, especially by the strongest evidence in breast and colorectal cancer.

The biological actions as anti-cancer effects of calcitriol are mostly exerted through genomic actions mediated by the VDR and its existence in the numerous tumor tissues is suggestive of its role in tumor genesis.The VDR is a member of the nuclear receptor/steroid hormone receptor superfamily. These receptors function as ligand-activated, transcriptional regulatory proteins.VDR/RXR complex translocates into the nucleus and induces the transcription of phosphoinositide phospholipase C-γ1 (PLC-γ1) through interaction with Vit.D responsive element (VDRE) on specific genes.

There is an up-regulation of VDR upon exposure to Vit.D. The anti-proliferative and pro differentiating effects of Vit.D are mostly mediated through the nuclear VDR.In many types of cancers, decreased VDR expression has been found in advanced neoplasms.It was demonstrated a differential expression of VDR (nuclear/cytoplasm) in progression of normal to invasive squamous cell carcinoma.

In this study, we aimed to detect tissue PDL-1, VDR expression levels and serum Vit.D levels as biomarkers for the early detection of LC, investigating the correlations between these biochemical indices and the clinicopathological features, and different risk factors in lung cancer patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: March 25, 2021
• Est. primary completion date: June 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

• newly diagnosed histopathologically proven stage I and II lung cancer.

Exclusion Criteria:

• : patients who have pulmonary secondaries or metastasis (usually multiple and widespread tumors), and who received treatment for lung cancer or those suffering from other malignancies elsewhere were excluded from the current study.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Other:
• Observational Study ( Tissue Biopsy )
control study includes a total of 90 subjects. Of them 54 patients with early stage lung (stage I, II) cancer (Group 1) were selected from the Chest Department of Assiut University Hospital, besides 36 healthy controls; who were clinically suspicious with chest masses and proven histopathologically to be negative cancer (Group 2).obtained by fiberoptic bronchoscopy

Locations

Country	Name	City	State
Egypt	Assiut University	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (3)

Ceeraz S, Nowak EC, Noelle RJ. B7 family checkpoint regulators in immune regulation and disease. Trends Immunol. 2013 Nov;34(11):556-63. doi: 10.1016/j.it.2013.07.003. Epub 2013 Aug 13. Review. — View Citation

Kim SH, Chen G, King AN, Jeon CK, Christensen PJ, Zhao L, Simpson RU, Thomas DG, Giordano TJ, Brenner DE, Hollis B, Beer DG, Ramnath N. Characterization of vitamin D receptor (VDR) in lung adenocarcinoma. Lung Cancer. 2012 Aug;77(2):265-71. doi: 10.1016/j.lungcan.2012.04.010. Epub 2012 May 6. — View Citation

Zhang Y, Jiang X, Li X, Gaman MA, Kord-Varkaneh H, Rahmani J, Salehi-Sahlabadi A, Day AS, Xu Y. Serum Vitamin D Levels and Risk of Liver Cancer: A Systematic Review and Dose-Response Meta-Analysis of Cohort Studies. Nutr Cancer. 2021;73(8):1-9. doi: 10.1080/01635581.2020.1797127. Epub 2020 Jul 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	measuring expression of PDL-1,VDR in cancer patients and healthy control.	we measured PDL-1 and VDR expressions by real time q-PCR, in lung cancer tissues from patients with stage I and II LC and healthy controls who were clinically suspicious with chest masses and proven histopathologically to be negative cancer .	through study completion, an average of 1 year.
Secondary	measuring serum Vit D level by EIA method	The level of serum Vitamin D (Vit.D) were assessed by EIA method.in lung cancer tissues from patients with stage I and II LC and healthy controls who were clinically suspicious with chest masses and proven histopathologically to be negative cancer .	through study completion, an average of 1 year.