Role of PD-L1 Expression in Non-Small Cell Lung Cancer and Their Prognostic Significance according to Clinicopathological Factors and Diagnostic Markers

Int J Mol Sci. 2019 Feb 14;20(4):824. doi: 10.3390/ijms20040824.

Abstract

Background: The latest immunotherapy, used in the treatment of non-small cell lung cancer (NSCLC), uses monoclonal antibodies directed against programmed death ligand 1 (PD-L1) to inhibit its interaction with the PD-1 receptor. Elevated levels of PD-L1 expression were observed on NSCLC cells. The association between PD-L1 expression and clinicopathological features is still unclear. Therefore, we examined this relationship and also compare PD-L1 expression levels with Ki-67, p63 and TTF-1.

Methods: 866 samples of NSCLCs were used to prepare tissue microarrays (TMAs) on which immunohistochemical (IHC) reactions were performed. Changes in the level of CD274 (PD-L1) gene expression in 62 NSCLC tumors were tested in relation to 14 normal lung tissues by real-time PCR reactions (RT-PCR).

Results: PD-L1 expression was observed in 32.6% of NSCLCs. PD-L1 expression was increased in higher malignancy grades (G) (p < 0.0001) and in higher lymph node status (pN) (p = 0.0428). The patients with low PD-L1 expression had longer overall survival compared to the group with high expression (p = 0.0332) in adenocarcinoma (AC) only.

Conclusions: PD-L1 expression seems to be associated with increased tumor proliferation and aggressiveness as well as shorter patient survival in NSCLC, predominantly in the AC group.

Keywords: Ki-67; PD-L1; TTF-1; non-small cell lung cancer; p63.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Aged
  • B7-H1 Antigen / genetics*
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ki-67 Antigen / genetics
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Prognosis
  • Thyroid Nuclear Factor 1 / genetics
  • Tissue Array Analysis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CKAP4 protein, human
  • Ki-67 Antigen
  • Membrane Proteins
  • Thyroid Nuclear Factor 1