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Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Comparative expression analysis of PD-1, PD-L1, and CD8A in lung adenocarcinoma
Ke Ma1, Yulei Qiao1, Hao Wang1
1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Background:
As a new strategy for advanced lung adenocarcinoma (LUAD), programmed cell death protein 1 (PD-1) pathway inhibitors have been used in clinic for several years. However, the roles of PD-1, programmed cell death-ligand 1 (PD-L1), and CD8A in LUAD are still unclear. In the study, we aimed to assess the correlation between the mRNA expression of these three factors and the clinical characteristics of LUAD, and to explore the influence of the PD-1/PD-L1/CD8A axis on the prognosis of LUAD.
Methods:
The mRNA expression data and clinical characteristics of LUAD patients were retrieved from The Cancer Genome Atlas (TCGA). The optimal cutoff value for PD-1, PD-L1, and CD8A was determined by Cutoff Finder. The chi-square test was used to compare categorical variables. The prognostic effects of variables were analyzed using the Kaplan---Meier method and the Cox proportional hazards model.
Results:
A total of 484 cases were enrolled in this study according to the selection process. The optimal cutoff values for identifying high/low mRNA expression were defined as 27.4 for PD-1, 29.41 for PD-L1, and 95.52 for CD8A. The high expression of PD-1 (P=0.015) and PD-L1 (P=0.027) was more frequent in women than in men. The high expression of PD-1 (P=0.003), PD-L1 (P=0.002), and CD8A (P=0.003) was associated with early T status, whereas CD8A showed a significantly higher expression in both the early stage (P=0.006) and early N stage groups (P=0.031). PD-1, PD-L1, and CD8A were significantly positively correlated among pairs (P<0.001). High expression of each of the three genes was associated with better prognosis (P=0.030 for PD-1, P=0.046 for PD-L1, P=0.019 for CD8A), although the relation did not reach statistical significance in the Cox regression hazards model.
Conclusions:
The study defined a group of cutoff values for PD-1, PD-L1, and CD8A to identify high and low mRNA expression in LUAD. The high expression of PD-1, PD-L1, and CD8A was associated with early T status, and CD8A showed significantly higher expression in both early stage and early N stage groups. Although the high expression of each of these three genes was associated with favorable overall survival (OS), they were not independent prognostic factors.
Insights
High expression of programmed cell death protein 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8A mRNA in lung adenocarcinoma (LUAD) correlates with earlier disease stages. While associated with better prognosis, these factors are not independent predictors of overall survival in LUAD patients.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Programmed cell death protein 1 (PD-1) pathway inhibitors are a strategy for advanced lung adenocarcinoma (LUAD).
- The specific roles of PD-1, programmed cell death-ligand 1 (PD-L1), and CD8A in LUAD require further clarification.
- Understanding the PD-1/PD-L1/CD8A axis is crucial for LUAD treatment and prognosis.
Purpose of the Study:
- To assess the correlation between mRNA expression of PD-1, PD-L1, and CD8A and LUAD clinical characteristics.
- To explore the impact of the PD-1/PD-L1/CD8A axis on LUAD patient prognosis.
- To establish optimal cutoff values for high and low mRNA expression of these genes in LUAD.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) for LUAD mRNA expression and clinical data.
- Determined optimal cutoff values for PD-1, PD-L1, and CD8A using Cutoff Finder.
- Employed chi-square tests, Kaplan-Meier, and Cox proportional hazards models for statistical analysis.
Main Results:
- Analyzed 484 LUAD cases; established cutoff values for PD-1 (27.4), PD-L1 (29.41), and CD8A (95.52).
- High PD-1 and PD-L1 expression was more frequent in women; all three genes showed higher expression in early T status.
- CD8A expression was significantly higher in early stage and N stage LUAD; all three genes positively correlated and were linked to better prognosis (though not independently).
Conclusions:
- Defined specific mRNA expression cutoff values for PD-1, PD-L1, and CD8A in LUAD.
- High expression of PD-1, PD-L1, and CD8A is associated with earlier T and N stages in LUAD.
- While high expression correlated with favorable overall survival, PD-1, PD-L1, and CD8A are not independent prognostic factors in LUAD.

