Association of PD-1, PD-L1, and CTLA-4 Gene Expression and Clinicopathologic Characteristics in Patients With Non-Small-Cell Lung Cancer.
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.



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.



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.



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.
Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, Alzira, Spain. Electronic address: alafuente@hospital-ribera.com.
Aránzazu
A
Lafuente-Sanchis
Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, Alzira, Spain.
Ángel
Á
Zúñiga
Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, Alzira, Spain.
Miriam
M
Estors
Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, Alzira, Spain.
Néstor J
NJ
Martínez-Hernández
Servicio de Anatomía Patológica, Hospital Universitario de la Ribera, Alzira, Spain.
Antonio
A
Cremades
Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, Alzira, Spain.
María
M
Cuenca
Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, Alzira, Spain; Área de Medicina y Cirugía respiratoria, Facultad de Medicina, Universidad Católica de Valencia, Valencia, Spain.
José M
JM
Galbis
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger
Clinicopathology; Immunotherapy; Inhibitory checkpoints; Predictive markers; Prognosis