The Role of Programmed Death Ligand -1 (Pdl-1) in Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Study type: Observational [Patient Registry]

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.
    

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.
    

Intervention name(s): Observational Study ( Tissue Biopsy )
Intervention type(s): Other
Intervention description(s): 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
Observational model: Case-Control
Time perspective: Cross-Sectional
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.