Association of PD-1, PD-L1, and CTLA-4 Gene Expression and Clinicopathologic Characteristics in Patients With Non-Small-Cell Lung Cancer.
INTRODUCTION
Recent studies show a potential benefit of therapies that target programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitory checkpoints in a subgroup of patients with non-small-cell lung cancer (NSCLC), without the clinicopathologic characteristics related to positive responses to these treatments being well determined. The aim of this study was to determine PD-1, PD-L1, and CTLA-4 gene expression at the mRNA level in tumoral tissue from patients with NSCLC and analyze their possible relationship with the clinicopathological characteristics and their potential prognostic role.


PATIENTS AND METHODS
PD-1, PD-L1, and CTLA-4 expression levels were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction in fresh-frozen tumor and normal adjacent lung tissue samples from 78 patients with NSCLC. Later, a significant association between mRNA levels, clinicopathologic characteristics, and patient's survival was assessed.


RESULTS
No significant correlation between gene expression levels and sex, age, histological type, smoking status, pathologic stage, or tumor differentiation was found. However, higher levels of PD-1 were significantly associated with worse prognosis in patients with NSCLC, and PD-L1 overexpression was associated with a worse prognosis in stage I patients and in Grade 1 to 2 tumors.


CONCLUSION
Alterations in PD-1/PD-L1 and CTLA-4 expression in lung tumoral tissue seem not to be related to age, sex, smoking status, histological type, pathological stage, or tumor differentiation degree. However, PD-1 and PD-L1 overexpression might predict worse survival in patients with stage I NSCLC and in well differentiated tumors.
['Lafuente-Sanchis|Aránzazu|A|', 'Zúñiga|Ángel|Á|', 'Estors|Miriam|M|', 'Martínez-Hernández|Néstor J|NJ|', 'Cremades|Antonio|A|', 'Cuenca|María|M|', 'Galbis|José M|JM|']
D000230:Adenocarcinoma D000368:Aged D060890:B7-H1 Antigen D014408:Biomarkers, Tumor D060908:CTLA-4 Antigen D018278:Carcinoma, Neuroendocrine D002289:Carcinoma, Non-Small-Cell Lung D002294:Carcinoma, Squamous Cell D005260:Female D006801:Humans D008175:Lung Neoplasms D008297:Male D060787:Neoplasm Grading D009367:Neoplasm Staging D011379:Prognosis D061026:Programmed Cell Death 1 Receptor D012333:RNA, Messenger D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction D015996:Survival Rate
Clinicopathology Inhibitory checkpoints Prognosis Immunotherapy Predictive markers