Correlation of PD-L1 Expression with Clinicopathological and Genomic Features in Chinese Non-Small-Cell Lung Cancer

Author:

Li Yue1ORCID,Li Chong2ORCID,Jiang Ya3ORCID,Han Xue3ORCID,Liu Sisi3ORCID,Xu Xiuxiu3ORCID,Tang Wanxiangfu3ORCID,Ou Qiuxiang3ORCID,Bao Hua3ORCID,Wu Xue3ORCID,Shao Yang3ORCID,Xing Minyan4ORCID,Zhang Yixiang5ORCID,Wang Yuezhen67ORCID

Affiliation:

1. Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150081 Harbin, Heilongjiang, China

2. Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China

3. Department of Research and Development, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China

4. Haining People’s Hospital, Haining, Zhejiang, China

5. Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medicine University, Dalian, Liaoning, China

6. Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China

7. Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China

Abstract

Programmed cell death 1 ligand 1 (PD-L1) has been approved as predictive biomarker for non-small-cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. The clinical/genomic features associated with PD-L1 are not well studied. Genomic profiling of tumor biopsies from 883 Chinese NSCLC patients was performed by targeted next-generation sequencing. Immunohistochemical analysis was conducted to evaluate PD-L1 expression levels using antibodies Dako 22C3 and 28-8, respectively. Our study showed distinct correlation between PD-L1 expression and clinical/genomic characteristics when using different PD-L1 antibodies and in different histological subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively. PD-L1 high expression (22C3) was associated with male and lymph node metastasis only in ADC patients. Furthermore, mutations of TP53 and KRAS, KIF5B-RET fusion, copy number gains of PD-L1 and PD-L2, and arm-level amplifications of chr.12p were significantly associated with PD-L1 positive status in ADC patients. For SCC patients, the gain of EGFR and MDM2 and loss of PTPRD were negatively associated with PD-L1 expression. We also compared our results with other studies and found conflicting results presumably because of the multiplicity of antibody clones and platforms, the difference of cutoffs for assigning PD-L1 expression levels, and the variation in study populations. Our study can help to understand the utility and validity of PD-L1 as biomarker of response to immune checkpoint inhibitors.

Funder

Natural Science Foundation of Zhejiang Province

Publisher

Hindawi Limited

Subject

Oncology

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