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

October 18, 2021 updated by: Norhan Salah Abd-Elmawgoud, Assiut University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Actual)

90

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Assiut, Egypt, 71515
        • Assiut University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The mean age ±S.E for controls was 55.47 ± 1.5 year, while that of lung cancer cases was 56.31 ± 0.83 years.

All patients were subjected to a full history taking, physical examination, routine laboratory investigations as blood picture, liver function, chest x- rays, chest ultrasonography. For patients who had been suspected clinically to have lung cancer, by examining the lung tissue obtained by fiberoptic bronchoscopic, the final diagnosis was confirmed histopathologically.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
case
54 patients with early stage lung (stage I, II) cancer (Group 1) were selected from the Chest Department of Assiut University Hospital,
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
control
besides 36 healthy controls; who were clinically suspicious with chest masses and proven histopathologically to be negative cancer (Group 2).
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
measuring expression of PDL-1,VDR in cancer patients and healthy control.
Time Frame: through study completion, an average of 1 year.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
measuring serum Vit D level by EIA method
Time Frame: through study completion, an average of 1 year.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2018

Primary Completion (Actual)

June 20, 2020

Study Completion (Actual)

March 25, 2021

Study Registration Dates

First Submitted

September 24, 2021

First Submitted That Met QC Criteria

October 5, 2021

First Posted (Actual)

October 19, 2021

Study Record Updates

Last Update Posted (Actual)

October 25, 2021

Last Update Submitted That Met QC Criteria

October 18, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PDL-1 Lung Cancer

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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