Prognostic Value of PD-L1 mRNA Sequencing Expression Profile in Non-Small Cell Lung Cancer

Ann Thorac Surg. 2018 Jun;105(6):1621-1626. doi: 10.1016/j.athoracsur.2018.01.081. Epub 2018 Mar 3.

Abstract

Background: Immune checkpoint inhibitors that target the programmed cell death protein ligand 1 (PD-L1) pathway have shown benefit for the treatment of metastatic non-small cell lung cancer (NSCLC). However, the prognostic value of PD-L1 independent of immunotherapy is still unclear, with conflicting results reported between PD-L1 expression and patient survival. Our aim was to correlate PD-L1 mRNA level with clinical and pathologic factors and to investigative the prognostic value of PD-L1 mRNA in all stages of NSCLC.

Methods: Gene expression and clinical data were obtained from public repositories in The Cancer Genome Atlas from the National Cancer Institute. Genotype-Tissue Expression was used to compare with normal tissue expression analysis.

Results: A total of 985 patients met inclusion criteria, among whom 79.6% were stage I to II, 16.5% were stage III, and 3.5% were stage IV, representing 495 adenocarcinoma and 490 squamous cell carcinoma (SCC). PD-L1 mRNA gene expression in lung cancers was higher than in most other tumor and normal tissue types and was significantly higher in lung SCC than adenocarcinoma (p < 0.001). PD-L1 mRNA expression was associated with pathologic stage in SCC and with smoking status in adenocarcinoma of the lung. However, none of the cutoff values of PD-L1 mRNA expression were prognostic of overall survival.

Conclusions: Our results suggest that the value of PD-L1 mRNA in prognosticating outcome in lung cancer is limited. Further studies are needed to identify novel prognostic biomarkers other than PD-L1 that are associated with improved patient survival. Identification of further prognostically important biomarkers may prove useful in identifying patients suitable for immunotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Cancer Care Facilities
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cohort Studies
  • Databases, Factual
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Linear Models
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics*
  • Proportional Hazards Models
  • RNA, Messenger / analysis
  • Reference Values
  • Risk Assessment
  • Survival Analysis
  • Texas

Substances

  • Programmed Cell Death 1 Receptor
  • RNA, Messenger