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Published on: September 25, 2018
[Correlation Study on Expression of PD-1 and PD-L1 in Non-small Cell Lung Cancer and Epidermal Growth Factor Receptor
Ling Jiang1, Zhiyi Lin1, Na Li2
1First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832002, China.
Background:
The treatment mode of lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for patients with EGFR mutant in non-small cell lung cancer (NSCLC). At the same time programmed death receptor 1 (PD-1) and its programmed death receptor ligand 1 (PD-L1) inhibitors therapy as the representative immune checkpoint inhibitors (ICIs) has a significant effect in the treatment of lung cancer. The aim of this study was to investigate the correlation between the expression of PD-1 and PD-L1 in NSCLC and clinicopathologic feature, EGFR gene mutation.
Methods:
The protein expression of PD-1 and PD-L1 was detected by immunohistochemistry from 127 patients with NSCLC and EGFR gene mutation was detected by quantitative polymerase chain reaction (qPCR) to analyze its relation with clinicopathologic feature. Also, the correlation between protein expression of PD-1 and PD-L1 and EGFR mutation.
Results:
The PD-1 positive expression in NSCLC tumor cells and tumor infiltrating immune cells is 53.5% (68/127), PD-L1 is 57.5% (73/127). The PD-1 and PD-L1 expression significantly higher in well-differentiated and moderately-differentiated carcinoma than poorly differentiated carcinoma, I+II than III+IV in clinical staging (P<0.05). The EGFR mutation rate was 46.5% (59/127), correlate with female, without smoking history, adenocarcinoma and well-differentiated and moderately-differentiated patients respectively higher than male, smoking history, squamous carcinoma and poorly differentiated patients (P<0.05). The protein expression of PD-L1 and PD-1 had the consistency in NSCLC patients (kappa=0.107,5, P=0.487). There was a negative correlation between the EGFR mutation and PD-1 and PD-L1 expression (Φ=-0.209, Φ=-0.221, P<0.05). Follow-up of NSCLC patients, the median total survival in under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, with PD-L1 expression patients respectively higher than over the age of 65, squamous carcinoma, poorly differentiated, without PD-L1 expression patients (P<0.05). The median survival of hypo expression patients of PD-L1 significantly higher than hyper expression patient (P=0.04).
Conclusions:
According to the Chinese Expert Consensus on Standards of PD-L1 immunohistochemistry testing for NSCLC, we tested the PD-L1 expression in NSCLC and then the dominant population of anti-PD-1/PD-L1 treatment was screened out. Patients with EGFR mutation were also detected and EGFR mutation was negatively correlated with the expression of PD-1 and PD-L1 as well. On the basis of PD-L1 expression and EGFR mutation status, it may benefit NSCLC patients from individualized treatment. Meanwhile, patients who were under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, hypo expression of PD-L1 have a relatively good prognosis, to provide reference for the prognosis evaluation of NSCLC.
Insights
Programmed death receptor 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) is negatively correlated with epidermal growth factor receptor (EGFR) mutations. Lower PD-L1 expression indicates a better prognosis for NSCLC patients.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) treatment involves epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutated patients.
- Immune checkpoint inhibitors (ICIs), such as programmed death receptor 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) inhibitors, are effective in lung cancer treatment.
Purpose of the Study:
- To investigate the correlation between PD-1 and PD-L1 expression in NSCLC.
- To analyze the relationship between PD-1/PD-L1 expression and clinicopathological features.
- To determine the association between PD-1/PD-L1 expression and EGFR gene mutations in NSCLC.
Main Methods:
- Detected PD-1 and PD-L1 protein expression using immunohistochemistry in 127 NSCLC patients.
- Quantified EGFR gene mutation status via quantitative polymerase chain reaction (qPCR).
- Analyzed correlations between protein expression, clinicopathological features, and EGFR mutation status.
Main Results:
- PD-1 and PD-L1 positive expression observed in 53.5% and 57.5% of NSCLC patients, respectively.
- Higher PD-1/PD-L1 expression correlated with better differentiation and earlier clinical stages (P<0.05).
- EGFR mutations were negatively correlated with PD-1 and PD-L1 expression (P<0.05); lower PD-L1 expression correlated with better prognosis.
Conclusions:
- EGFR mutation is negatively correlated with PD-1 and PD-L1 expression in NSCLC.
- PD-L1 expression and EGFR mutation status can guide individualized NSCLC treatment strategies.
- Patients with lower PD-L1 expression, younger age, adenocarcinoma, and better differentiation show a better prognosis.
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