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.
Background: The activation of inflammation and coagulation cascades plays an essential role in the development of various malignancies, including metastatic breast cancer (MBC). This retrospective study aimed to investigate the prognostic role of the combination of fibrinogen and the inflammation-based index in patients with MBC.Methods: A total of 176 patients with MBC were retrospectively reviewed. The clinical and pathological data of included patients were followed-up and analyzed. The plasma fibrinogen concentration (FIB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were measured. Dynamic variations in the FIB, NLR, and PLR values were collected from 56 MBC patients before and after firstline therapy. Receiver operating characteristic (ROC) curves were constructed to assess the optimal cut-off values. Correlations between FIB and NLR or PLR were evaluated using Spearman correlation analysis. The Kaplan-Meier method, two-tailed log-rank test, and Cox proportional hazard model were used for statistical analysis.Results: Baseline FIB was positively correlated with NLR and PLR values in MBC patients (P<0.05).Additionally, multivariable analysis proved that the ERBB2 + subtype (P=0.023), basal-like subtype (P=0.032), targeted therapy (P=0.033), other regimens (P=0.005), and baseline FIB level (P=0.004) were independent prognostic variables for progression-free survival (PFS) in MBC patients. Furthermore, ERBB2+, basal-like subtypes, and baseline hyperfibrinogenemia were independent factors for poor prognosis in MBC patients
Background: The acquisition of radioresistance by nasopharyngeal carcinoma (NPC) cells during radiotherapy may lead to tumor metastasis and poor survival. This study aimed to explore the mechanism of long-term radiation-induced NPC metastasis. Methods:The radioresistant NPC cell, Hone-1R, was established for further study. A colony-forming assay was selected for the evaluation of radioresistant capacity, while a scratch wound healing assay was used to detect tumor cell migration. The expression of relative protein levels were detected by Western blot (WB) analysis and immunofluorescence. Cell morphology was acquired by microscopy. The programmed cell death ligand-1 (PD-L1) expression level in NPC tumor tissues was evaluated based on the publicly available datasets of NPC patients.Results: A radioresistant NPC cell, Hone-1R, was established with a total dose of 180 Gy, and verified by radioresistant capacity testing. The morphology of Hone-1R cells showed obvious mesenchymal-like cells.WB and wound healing assays indicated that Hone-1R cells exhibited an epithelial-mesenchymal transition (EMT) phenotype with high migration ability and upregulation of PD-L1. Knockdown of PD-L1 reversed EMT status and reduced the migration ability of Hone-1R cells. Further analysis indicated that PD-L1 was overexpressed in more advanced stages and was positively correlated with the EMT score in NPC patients based on in silico analysis.Conclusions: Our study revealed that long-term radiation induces EMT and increases migration ability of NPC radioresistant cells through upregulation of PD-L1. These results advance our investigation of the underlying mechanism of ionizing radiation (IR)-induced migration, and suggest potential interventions to reverse EMT-induced acquisition of radioresistance in NPC.
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