title: Induction of Patient-Derived Xenograft Formation and Clinical Significance of Programmed Cell Death Ligand 1 (PD-L1) in Lung Cancer Patients.
abstract: BACKGROUND The immune checkpoint of programmed cell death ligand 1 (PD-L1) commonly expressed in solid cancers, and the blockade of this molecule show promising results in advanced cancers, including lung cancer. The relevance of PD-L1 to patient-derived xenograft (PDX) formation and clinicopathological characteristics in early stage lung cancer have not been fully elucidated. MATERIAL AND METHODS Cell counting kit-8 and flow cytometry were carried out to examine proliferation and apoptosis in PC9 and H520 cells transfected with siRNAs. Nod-scid mice were used to establish PDX. Immunohistochemistry was done to investigate PD-L1 expression in tumor tissues. RESULTS PD-L1 was detected in lung cancer cell lines and 45.45% of primary tumor tissues from a cohort of 209 lung cancer patients. Cell growth was restrained and apoptosis was induced when PD-L1 was inhibited in PC9 and H520 cells. In addition, we successfully established 16 PDX models from tissues from 43 cases of primary lung cancer. Higher PD-L1 expression rates (75%) was observed in primary tumors with PDX formation compared to protein expression rate (44.44%) in tumors without PDX formation. Consistently, a 1.9-fold increase of PDX formation frequency was identified in the PD-L1 positive tumors than in the PD-L1 negative tumors. Moreover, PD-L1 was found to be related to smoking, histological type, and pathological stage. Importantly, PD-L1 overexpression was associated with shorter overall survival (OS) of lung cancer patients. CONCLUSIONS This study suggests that overexpression of PD-L1 could induce PDX formation and is related to poor outcome for the lung cancer patients.
authors: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Yuanyuan
authors: Y
authors: Ma
authors: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Panpan
authors: P
authors: Zhang
authors: Department of Laboratory Animal, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Guo
authors: G
authors: An
authors: Department of Laboratory Animal, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Xiaolong
authors: X
authors: Zhang
authors: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Liyi
authors: L
authors: Zhang
authors: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Jiahui
authors: J
authors: Si
authors: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Jianzhi
authors: J
authors: Zhang
authors: Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China (mainland).
authors: Yue
authors: Y
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D012189:Retrospective Studies; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D066246:ErbB Receptors