Jin Li1,2, Yaoqi Chen1,2, Xiaoshun Shi1,2, Xiaobing Le3, Fenglan Feng1, Jingyi Chen1, Chengzhi Zhou1,2, Yusong Chen1,2, Shuai Wen1,2, Haikang Zeng1,2, Allen M Chen4, Yu Zhang3. 1. State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China. 2. National Clinical Research Center for Respiratory Disease, Guangzhou 510120, China. 3. Institute of Life Science, Nanchang University, Nanchang 330000, China. 4. Department of Mathematics, University of California, Berkeley 94720, CA, USA.
Abstract
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed. We performed meta-analysis for data included in the selected literature, and then independently explored the correlation between genes by co-expression analysis of RNA-seq data in the TCGA database. RESULTS: A sum of 9,934 lung cancer cases were collected from 34 published studies. Higher PD-L1 expression was associated with wild-type epidermal growth factor receptor (EGFR) [odds ratio (OR): 0.68, 95% confidence interval (CI): 0.48-0.96, P=0.03], Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (OR: 1.27, 95% CI: 1.02-1.58, P=0.03) or non-adenocarcinoma histology (OR: 0.68, 95% CI: 0.47-0.98, P=0.04). In addition, our analysis from TCGA data indicated that, compared with lung adenocarcinoma, the expression of PD-L1 was significantly higher than that of squamous cell carcinoma patients (P=0.023). The expression of targetable driver genes showed no correlations with PD-L1 expression in non-small cell lung cancer (NSCLC). CONCLUSIONS: Our results suggest the presence of EGFR wild-type, KRAS gene mutations or squamous cell carcinoma were associated with high PD-L1expression, which provides potential benefited population for the administration of PD-1/PD-L1 blockade in human lung cancer.
BACKGROUND: Studies have shown that the ligand of programmed cell death protein 1 (B7-H1, CD274 or PD-L1) is related to lung cancer driver genes. Although studies have examined the association between lung cancer driver gene mutations or expression and PD-L1 expression, the present studies have not been mined the correlation systematically and genome-widely. METHODS: All relevant published PD-L1 articles with driver genes data and the RNA-seq dataset from The Cancer Genome Atlas (TCGA) were analyzed. We performed meta-analysis for data included in the selected literature, and then independently explored the correlation between genes by co-expression analysis of RNA-seq data in the TCGA database. RESULTS: A sum of 9,934 lung cancer cases were collected from 34 published studies. Higher PD-L1 expression was associated with wild-type epidermal growth factor receptor (EGFR) [odds ratio (OR): 0.68, 95% confidence interval (CI): 0.48-0.96, P=0.03], Kirsten ratsarcoma viral oncogene homolog (KRAS) mutation (OR: 1.27, 95% CI: 1.02-1.58, P=0.03) or non-adenocarcinoma histology (OR: 0.68, 95% CI: 0.47-0.98, P=0.04). In addition, our analysis from TCGA data indicated that, compared with lung adenocarcinoma, the expression of PD-L1 was significantly higher than that of squamous cell carcinomapatients (P=0.023). The expression of targetable driver genes showed no correlations with PD-L1 expression in non-small cell lung cancer (NSCLC). CONCLUSIONS: Our results suggest the presence of EGFR wild-type, KRAS gene mutations or squamous cell carcinoma were associated with high PD-L1expression, which provides potential benefited population for the administration of PD-1/PD-L1 blockade in humanlung cancer.
Entities:
Keywords:
Programmed death-ligand 1 (PD-L1); The Cancer Genome Atlas (TCGA); driver genes; immunotherapy; non-small cell lung cancer (NSCLC)
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