Boris Sepesi1, David B Nelson2, Kyle G Mitchell2, Don L Gibbons3, John V Heymach3, Ara A Vaporciyan2, Stephen G Swisher2, Jason Roszik4. 1. Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: bsepesi@mdanderson.org. 2. Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. 3. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 4. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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.
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.
Authors: Anna Grenda; Marcin Nicoś; Michał Szczyrek; Paweł Krawczyk; Tomasz Kucharczyk; Bożena Jarosz; Juliusz Pankowski; Marek Sawicki; Justyna Szumiło; Paulina Bukała; Janusz Milanowski Journal: Oncol Lett Date: 2019-04-03 Impact factor: 2.967