Abstract
Purpose
The study aimed to evaluate the clinicopathological and molecular profiles associated with programmed death ligand 1 (PD-L1) expression in non-small cell lung cell (NSCLC) in a large-scale, multi-center, real-world Chinese cohort.
Methods
A total of 6295 NSCLC specimens from six centers in China were analyzed by PD-L1 (22C3) assay. PD-L1 expression in tumor cells (TCs) was classified as negative (TPS expression in < 1% of TCs), low (TPS in 1–49% of TCs), or high (TPS in ≥ 50% of TCs). The status of EGFR mutation was determined by reverse transcription polymerase chain reaction or next-generation sequencing, and ALK and ROS1 translocation was analyzed by immunohistochemistry and fluorescence in situ hybridization. Associations of PD-L1 expression with clinicopathological features and driver mutations were analyzed.
Results
Positive PD-L1 expression was more frequently seen in squamous cell carcinoma (SCC) and other histological types of NSCLC compared to adenocarcinoma (AC). In AC, PD-L1 expression was associated with gender, histological type, metastatic status, and pathological features of lymphovascular invasion and visceral pleural invasion. Solid and micropapillary subtypes of AC were more likely to have positive PD-L1 expression compared to other subtypes. PD-L1 was more highly expressed in biopsy samples than in resected samples, and in metastatic samples compared with primary tissues. PD-L1 expression was significantly associated with wild-type EGFR and ALK translocations.
Conclusions
PD-L1 expression in NSCLC is linked to histological type, pathological features, and driver mutation status, which has meaningful implications for clinical practice.
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Availability of data and materials
All data relevant to the study are included in the article and uploaded as supplementary information.
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Acknowledgments
Editorial assistance and proofreading were provided by Medjaden Bioscience Limited. Funding for this assistance service was provided by MSD China.
Funding
This study was supported by National Nature Science Foundation of China grant number 81972171 and 81472173.
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XC, CW, YL conceived, designed and planned the study. YH, XZ, XC, QX, YW, YG and BG provided study materials and patients. CW provided administrative and technical support. QZ, YH, XC, XZ, SS, YJ, QX, YW, YG and BG collected the data. QZ and YH performed analyses. YW performed statistical expertise. QZ and CW interpreted the results. QZ, XC, QX, YW and YL wrote the initial draft. QZ, YH, XZ, SS, CW, YJ, QX, YG, BG and YL provided suggestions for revision of the manuscript. All authors reviewed and approved final version of the paper.
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The study was approved by the Institutional Review Board of Fudan University Shanghai Cancer Center. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Zheng, Q., Huang, Y., Zeng, X. et al. Clinicopathological and molecular characteristics associated with PD-L1 expression in non-small cell lung cancer: a large-scale, multi-center, real-world study in China. J Cancer Res Clin Oncol 147, 1547–1556 (2021). https://doi.org/10.1007/s00432-020-03444-y
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DOI: https://doi.org/10.1007/s00432-020-03444-y