The Prognostic Significance of PD1 and PDL1 Gene Expression in Lung Cancer: A Meta-Analysis

Abstract

BackgroundImmune checkpoint blockade therapy represents an extraordinary advance in lung cancer treatment. It is important to determine the expression of immune checkpoint genes, such as programmed cell death 1 (PD1) and programmed cell death-ligand 1 (PDL1), to develop immunotherapeutic strategies. The aim of this study was to explore the association between PD1 and PDL1 gene expression and prognoses and outcomes in lung cancer.MethodsThis meta-analysis analyzed 1,251 patients from eight different microarray gene expression datasets and were evaluated for their prognostic implications and verified using another independent research.ResultsThe mean expression levels of PDL1 in adenocarcinoma (AD) and squamous cell carcinoma (SC) were significantly higher in patients who died than in patients who did not. There was a trend toward incremental increases in PD1 and PDL1 expression significantly decreasing the risk of relapse and death among AD patients (HR = 0.69; 95% CI = 0.53 ~ 0.91; HR = 0.68; 95% CI = 0.54 ~ 0.84, respectively) and SC patients (HR = 0.53; 95% CI = 0.32 ~ 0.89; HR = 0.78; 95% CI = 0.57 ~ 1.00 respectively), as early-stage patients in this study were more likely to have high expression of both PD1 and PDL1 than late-stage patients (P-trend < 0.05). In contrast, late-stage SC patients expressing one or more of the genes at a high level had a significantly elevated risk of relapse (HR = 1.51; 95% CI = 1.07 ~ 2.11) and death (HR = 1.41; 95% CI = 1.08 ~ 1.84). This result was consistent with the validation data set.ConclusionThese findings indicate that high expression of PD1 and PDL1 is associated with superior outcome in early-stage lung cancer but an adverse outcome in late-stage lung cancer. The expression levels of PD1 and PDL1 individually or jointly are potential prognostic factors for predicting patient outcomes in lung cancer.

The detection of PD‐L1 expression on liquid‐based cytology in pleural effusion of lung adenocarcinoma and its prognostic evaluation: Between paired liquid‐based cytology and cell block samples

“…27 They can inhibit the proliferation of CD8+ T cells, which may be an important reason for promoting tumor progression. Most studies support that tumors with PD-L1-positive expression have a worse prognosis, 8,28,29 which might be related to the increased proportion of mesenchymal cells and their secreted inflammatory factors. The high PD-L1 expression was associated with increased NLR ( p = .011), involving increased neutrophils and decreased lymphocyte proportion.…”

Influence of PD‐L1 expression on the efficacy of EGFR‐TKIs in EGFR‐mutant non‐small cell lung cancer

“…Studies regarding the prognostic or predictive value of PD‐L1 expression in NSCLC can be divided into different types according to the scope of the target population, including those focusing on the whole NSCLC population, 16–18 or EGFRm population, 19–22 or EGFRm population treated with EGFR ‐TKIs 12–15,23–34 as in the current study. In addition, there have also been studies which have investigated the value of PD‐L1 expression on mRNA level 35 . The majority of these studies have concluded that higher PD‐L1 expression is associated with shorter survival time in EGFRm patients or quicker development of EGFR ‐TKI resistance.…”

Establishment of an ovarian cancer omentum metastasis-related prognostic model by integrated analysis of scRNA-seq and bulk RNA-seq

“…The immune checkpoint analysis displayed seemingly contradictory results between expression level and prognosis; however, research has also shown that high expression of PD1 and PD-L1 is associated with favorable outcome in lung cancer of early-stage but an adverse outcome in late-stage [ 34 ]. The ratio of stage I-II patients in cluster 3 was much higher than that in cluster 2, and it might be the dual effect of PD1 and PD-L1 on prognosis that leads to this result.…”