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
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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