Prognostic significance of PD‐L1 expression on cell‐surface vimentin‐positive circulating tumor cells in gastric cancer patients
Autor: | Yuting Liu, Fuguang Wang, Mengyuan Liu, Xuren Sun, Tong Zhao, Ruoyu Wang, Gang Wang, Mingjun Sun, Jin Yan, Zhi Wang, Guan Wang, Heming Li, Xiangyu Kong, Qiuge Liu, Shanshan Liang, Weipeng Lv, Qingfu Zhang, Liang Chen, Xuening Ji |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Cancer Research medicine.drug_class Vimentin circulating tumor cells Monoclonal antibody Immunofluorescence epithelial–mesenchymal transition lcsh:RC254-282 B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Circulating tumor cell Stomach Neoplasms Genetics medicine Biomarkers Tumor Humans Epithelial–mesenchymal transition Research Articles biology medicine.diagnostic_test business.industry gastric cancer Cancer programmed cell death ligand 1 General Medicine Middle Aged medicine.disease Neoplastic Cells Circulating Prognosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology cell‐surface vimentin Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Molecular Medicine Immunohistochemistry Female business CD8 Research Article |
Zdroj: | Molecular Oncology, Vol 14, Iss 4, Pp 865-881 (2020) Molecular Oncology |
ISSN: | 1574-7891 1878-0261 |
Popis: | Although circulating tumor cells (CTCs) have shown promise as potential biomarkers for diagnostic and prognostic assessment in gastric cancer (GC), determining the predictive and prognostic value of programmed death‐ligand 1 (PD‐L1)‐positive CTCs in patients with GC is a challenge. Here, we identified that the expression of total vimentin (VIM) protein was positively correlated with PD‐L1 and inhibited CD8+ T‐cell activation in patients with GC according to bioinformatics analysis. Notably, coexpression of PD‐L1 and cell‐surface VIM (CSV) was detected by immunofluorescence and immunohistochemistry assay in locally advanced GC tumor specimens and metastatic lymph nodes. Likewise, CSV expression level was significantly decreased after transiently knocking down PD‐L1 in GC cell lines. Based on our established CTC detection platform, CTCs were isolated from peripheral blood samples collected from 70 patients (38 resectable and 32 unresectable) with GC using magnetic positive selection and a CSV‐specific monoclonal antibody, 84‐1. CSV+PD‐L1+CTCs were observed in 50 of 70 (71%) GC patient samples, ranging from 0 to 261 mL−1. A higher number of CSV+PD‐L1+CTCs were significantly associated with a short survival duration and poor therapeutic response. This study demonstrated that detection of PD‐L1+CTCs using a CSV‐enrichment method has promising value as a clinically relevant prognostic marker for GC. CSV+PD‐L1+CTC exhibits epithelial mesenchymal transition subtype, which can be observed in GC patient’s peripheral blood samples. A higher number of CSV+PD‐L1+CTCs are significantly associated with a short survival duration and poor therapeutic response. |
Databáze: | OpenAIRE |
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