Humans ; B7-H1 Antigen ; Neoplasms/genetics*

OBJECTIVE: To investigate the expression and clinical significance of PD-L1 and microRNA-138-5p in the peripheral blood mononuclear cells of patients with acute myeloid leukemia. METHODS: The SYBR GreenⅠreal-time PCR was used to detect the expression levels of PD-L1 mRNA and miR-138 in 20 cases of primary AML, 9 cases of relapsed/refractory AML and 8 cases of complete remission. The samples of peripheral blood of 20 healthy peoples were used as controls. RESULTS: The expression levels of PD-L1 in both the primary AML and the relapsed/refractory AML groups were significantly higher than those in the healthy control group (P<0.01), and the expression level of PD-L1 in the relapsed/refractory AML group was significantly higher than that in the primary AML group (P<0.01). The expression level of miR-138 in both the primary AML and the relapsed/refractory AML groups were significantly lower than that in the healthy control group (P<0.01). The 8 sampes out of 20 cases of primary AML patients achieved complete remission (CR) were collected and detected. The results showed that the expression level of miR-138 in the complete remission group was higher than that in the primary AML group (P<0.05), but the expression level of PD-L1 mRNA in the CR group was not significantly different from that in the primary AML group (P>0.05). and there was a negative correlation between PD-L1 mRNA and miR-138 in primary AML patients (P<0.05). CONCLUSION The expression of PD-L1 increases and the expression of miR-138 down-regulates in PBMNCs of AML patients, furthermore, both correlate each other.
B7-H1 Antigen ; genetics ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Leukocytes, Mononuclear ; MicroRNAs ; genetics ; Remission Induction

OBJECTIVE: To explore the regulatory role of miR-4772 in the formation of tumor immune microenvironment in ovarian cancer. METHODS: The optimal cutoff level of PD-L1 expression was calculated based on data from 294 ovarian cancer patients in the TCGA database. The differentially expressed genes (DEGs) between high and low PD-L1 expression groups were screened, and the important DEGs were identified by correlation analysis. WGCNA analysis was performed to select the weighted genes and PD-L1-related miRNAs, from which the hub genes were obtained by intersection analysis. ssGSEA analysis was used to evaluate the effect of PD-L1 and miR-4772 expressions on the tumor immune microenvironment in ovarian cancer. KEGG analysis was used to identify the involved signal pathways, and the interactions between the hub genes were mapped by protein-protein interaction (PPI) analysis. Survival analysis was carried out to identify the survival-related hub genes, and the results were validated using the data of 399 patients with ovarian cancer from GEO database and the sequencing results of SKOV3 cells transfected with miR-4772 mimics or inhibitor. RESULTS: According the optimal cutoff level of PD-L1 expression of 1.31582 (90th quantile), the patients were divided into high- and low-PD-L1 expression groups. A total of 840 DEGs were identified, including 549 significantly up-regulated genes and 291 down-regulated genes. Among them, 20 important DEGs were found to closely correlate with miR-4772 expression, and WGCNA analysis identified 48 weighted genes significantly correlated with miR-4772. Twelve genes were identified as both key DEGs and weighted genes and were treated as the hub genes. ssGSEA analysis showed that both the patients with high PD-L1 expressions and those with high miR-4772 expressions showed more active immune infiltration and functional activity. The 12 hub genes were involved mainly in immune-related signaling pathways, and PPI analysis suggested significant interactions among the hub genes. The two hub genes CD96 and TBX21 showed close correlation with the survival of ovarian cancer patients. The sequencing results of SKOV3 cells transfected with miR-4772 mimics or inhibitor showed that the changes in miR-4772 expression level caused obvious changes in the expressions of the 12 hub genes and PD-L1. CONCLUSION MiR-4772 plays a regulatory role in the formation of tumor immune microenvironment in ovarian cancer by regulating 12 hub genes.
Humans ; Female ; B7-H1 Antigen/genetics* ; Tumor Microenvironment ; Ovarian Neoplasms/genetics* ; MicroRNAs/genetics* ; Databases, Factual

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).
B7-H1 Antigen/genetics* ; Humans ; Immunohistochemistry ; Prognosis ; Triple Negative Breast Neoplasms/pathology*

This study investigated the effect of etoposide, an anticancer chemotherapy drug, on B7-H1 expression in retinoblastoma (Rb) cells and the role of miR-513a-5p in the process. Rb cells were divided into control and etoposide groups. In the etoposide group, cells were treated with etoposide at different concentrations (2.5, 5, 10, 20 and 40 μg/mL) for 24 h. Those given no treatment of etopside served as controls. Reverse transcription polymerase chain reaction (RT-PCR), fluorescence quantitative PCR and flow cytometry were performed to measure the mRNA and protein expression of B7-H1 in Rb cells. The mRNA expression of miR-513a-5p in Rb cells before and after etoposide treatment was also detected by fluorescence quantitative PCR. The miR-513a-5p mimics and the miR-513a-5p inhibitor were transfected into Rb cells separately, and fluorescence quantitative PCR and flow cytometry were used to detect the effect of the miR-513a-5p mimics or inhibitor on B7-H1 expression. TargetScan5.2 was employed to predict the miR-513a-5p binding sites in the 3'-untranslated region of B7-H1 mRNA. Luciferase reporter plasmids carrying this site were prepared and transfected into Rb cells and luciferase activity analyzed. The results showed that etoposide stimulated the mRNA and protein expression of B7-H1 in Rb cells, which reached a maximal level after treatment with 5 μg/mL etoposide (P<0.05). However, miR-513a-5p expression was decreased in Rb cells after etoposide treatment. When the miR-513a-5p inhibitor was added, B7-H1 expression was increased with the concentration of the miR-513a-5p inhibitor (P<0.05). Moreover, B7-H1 expression was decreased gradually with the concentration of the miR-513a-5p mimics increased (P<0.01). Additionally, the miR-513a-5p mimics were found to inhibit the luciferase activity. It was concluded that etoposide can promote B7-H1 expression in Rb cells, which may be associated with chemoresistance. The promoting effect of etoposide on B7-H1 expression can be reversed by miR-513a-5p mimics. MiR-513a-5p inhibits the mRNA and protein expression of B7-H1 via binding to the 3'-UTR of B7-H1 mRNA.
B7-H1 Antigen ; genetics ; Cell Line, Tumor ; Etoposide ; pharmacology ; Gene Expression ; drug effects ; genetics ; Humans ; MicroRNAs ; genetics ; Retinoblastoma ; genetics

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors were landmarks in the treatment of non-small cell lung cancer (NSCLC). However, the regulation mechanisms of PD-L1 expression were not fully clear in NSCLC patients with EGFR mutations. Multiple signaling pathways may be involved in the tumorigenesis regulation. This paper summarized and reviewed the potential EGFR mutations impacting on PD-L1 expression with aims to the development of strategies on immunochemical therapy for NSCLC.
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Adenocarcinoma of Lung ; genetics ; pathology ; B7-H1 Antigen ; metabolism ; ErbB Receptors ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Signal Transduction ; genetics

OBJECTIVES: To explore the expression of programmed death ligand-1 (PD-L1) as well as the correlation between the expression and the clinicopathological features or prognosis in non-small cell lung cancer (NSCLC). METHODS: The expression of PD-L1 protein in 254 cases of surgically resected lung adenocarcinoma (L-ADC), 228 cases of surgically resected lung squamous cell cancer (L-SCC), and 99 cases of non-cancerous control lung tissues was detected with immunohistochemical SP method. The correlation between the PD-L1 expression and clinicopathological features was analyzed. Kaplan-Meier univariate and Cox multivariate regression analyses were performed to assess the prognosis of patients with L-ADC and L-SCC, respectively. RESULTS: Positive percentage of PD-L1 protein expression was higher in the tissues of L-ADC and L-SCC than that in the non-cancerous control lung tissues respectively (both CONCLUSIONS The positive percentage of PD-L1 protein expression is higher in the L-SCC patients than that in the L-ADC patients. Positive expression of PD-L1 protein can be served as an independent prognostic factor of poor prognosis in the patients with L-ADC.
Adenocarcinoma of Lung ; B7-H1 Antigen/genetics* ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/surgery* ; Humans ; Lung Neoplasms/surgery* ; Patients ; Prognosis

The clinical application of immune checkpoint inhibitors (ICIs) lead to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC), but the efficacy of ICIs in oncogene-driven NSCLC is controversial. Existing research shows that the efficacy of ICIs may be related to different types of driver genes, programmed cell death-ligand 1 (PD-L1) level, and tumor mutational burden (TMB). It may involved in other factors, such as clinical characteristics, and immune cell density. ICIs monotherapy or combination therapy may play a role in a subset of oncogene-driven NSCLC patients, but further studies are needed to select these patients, which may be an important direction for the future development of advanced NSCLC.
B7-H1 Antigen ; genetics ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Immunotherapy ; Lung Neoplasms ; drug therapy

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression. METHODS: Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis. RESULTS: The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05). CONCLUSION Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.
B7-H1 Antigen ; Carcinoma, Squamous Cell/genetics* ; Esophageal Neoplasms/genetics* ; Esophageal Squamous Cell Carcinoma/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation/genetics*

Animals ; Antigens, CD ; biosynthesis ; genetics ; immunology ; B7-H1 Antigen ; CD28 Antigens ; biosynthesis ; genetics ; Humans ; Immune Tolerance ; Liver ; immunology ; RNA, Messenger ; biosynthesis ; genetics ; T-Lymphocytes ; immunology