29126

CD274

CD274 molecule;CD274;CD274 molecule

B7 homolog 1|CD274 antigen|PDCD1 ligand 1|programmed cell death 1 ligand 1|programmed death ligand 1

9p24

protein-coding

OBJECTIVE: To study the expression of ligand 1 of programmed death-1 (PD-L1) in human laryngocarcinoma tissues and peritumoral tissue and its potential significance to clinic. METHOD: Immunohistochemistry and Western-blotting were performed to assess the expression of PD-L1 at protein level and the differences in 31 cases of laryngocarcinoma tissue and 24 cases of paraneoplastic tissue. RESULT: expression of PD-L1 was significantly higher in poorly and moderately differentiated larynx squamous carcinoma than that in well differentiated larynx squamous carcinoma. The expression of PD-L1 in the former was mainly in blood vessels while rarely in cancer cells, and the blood vessel of the latter displayed weakly positive while partial cancer cells showed positive; and the expression of PD-L1 was significantly correlated with lymphatic metastasis. expression of PD-L1 in paraneoplastic tissues was significantly lower than that in cancer tissues but positively correlated to the expression level in the cancer tissues. CONCLUSION: PD-L1 may play a part in the development and/or metastasis of laryngocarcinoma, particularly in the bad differentiated; And it maybe a new target of immunotherapy for laryngocarcinoma, especially for the poorly and moderately differentiated.

Patients with neuroblastoma due to N-Myc oncogene amplification have a high frequency of tumor metastasis. However, it is not clear how N-Myc induces cell migration, invasion and metastasis. The histone demethylase JMJD1A activates gene transcription by demethylating the lysine 9 residue of histone H3 (H3K9) at target gene promoters. The long noncoding RNA MALAT1 induces lung cancer cell migration and plays a pivotal role in lung cancer metastasis. Here we demonstrated that N-Myc up-regulated the expression of JMJD1A in N-Myc oncogene-amplified human neuroblastoma cells by directly binding to the JMJD1A gene promoter. Affymetrix microarray studies revealed that the gene second most significantly up-regulated by JMJD1A was MALAT1. Consistent with this finding, RT-PCR and chromatin immunoprecipitation assays showed that JMJD1A bound to the MALAT1 gene promoter and demethylated histone H3K9 at the MALAT1 gene promoter. Moreover, JMJD1A and MALAT1 induced, while the small molecule JMJD1A inhibitor DMOG suppressed, neuroblastoma cell migration and invasion. Taken together, our data identify a novel pathway through which N-Myc causes neuroblastoma cell migration and invasion, and provide important evidence for further development of more potent JMJD1A/MALAT1 inhibitors for the prevention of tumor metastasis.

OBJECTIVE: To investigate the expression of ligand 1 of programmed death-1 in human nasopharyngeal carcinoma (NPC), the relationship between their expression and the clinicopathological features. METHOD: Immunohistochemistry was performed to assess the expression of PD-L1 in 59 cases of NPC tissues and 10 cases of normal nasopharyngeal tissue. RT-PCR was used to investigate the mRNA expression of PD-L1 gene in 30 NPC samples and 10 cases of normal nasopharyngeal tissues. RESULT: In case of tissues of nasopharyngeal carcinoma, the positive expression rate of PD-L1 protein and PD-L1mRNA were 67.8% (40/59) and 66.6% (20/30) respectively, while there were no PD-L1 detectable in normal nasopharyngeal tissues. The expression of PD-L1 was significantly correlated with clinical TNM stage and lymphatic metastasis (P <0.05). However, no significant correlation was founded between the expression of PD-L1 and age and sex (P >0.05). CONCLUSION: PD-L1 is overexpressed in nasopharyngeal carcinoma, PD-L1 maybe play a certain role in carcinogenesis and progression of nasopharyngeal carcinoma and turn into a new target of immunotherapy of nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the correlation between programmed death-ligand 1 (PD-L1) expression in primary lung cancer cells, tumor associated macrophages (TAM) and patients' clinicopathological characteristics. METHODS: From 2008 to 2010, 208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital, Fudan University. Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM. The relationship between PD-L1 expression and the clinical pathology was evaluated using chi(2) test. Spearman's rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages. RESULTS: Positive PD-L1 expression in primary cancer cells was found in 136 (65.3%) patients, which were negatively correlated with lymph node metastasis (P=0.009) and smoking history (P=0.036). Besides, TAM with PD-L1 expression (found in 116 patients) was positively associated with smoking history (P=0.034), well-differentiation (P=0.029) and negative lymph node metastasis (P=0.0096). A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found (r=0.228, P=0.021). CONCLUSION: PD-L1, secreted from TAM, might induce cancer cells apoptosis, and decrease lymph node metastasis.

BACKGROUND: cancer cells develop mechanisms to evade immune cells and achieve progression. Aberrant B7-H1 and B7-1 expressions may help pancreatic carcinoma (PC) cells escape immune attack; these molecules can be considered as prognostic markers for patients with PC who have undergone radical resection. METHODS: We recruited 81 patients who had undergone radical surgical resection for PC between 1999 and 2007. To investigate the prognostic factors, we evaluated the B7-H1 and B7-1 protein expressions in the tissue specimens of these 81 patients by immunohistochemistry and analyzed the clinical and pathological features of these specimens. RESULTS: B7-H1 was expressed mainly in pancreatic islets, and no B7-1 expression was detected in normal pancreatic tissues. B7-H1 and B7-1 expressions were higher in pancreatic carcinoma tissues than in normal pancreatic tissues (P < 0.05). B7-H1 and B7-1 significantly correlated with the pathological grade and tumor-node-metastasis (TNM) stage, respectively (P < 0.05). Furthermore, B7-1-negative or B7-H1-positive statuses were prognostic indicators of poor disease-specific survival (P < 0.05), but only combined B7-1/B7-H1 expression retained the prognostic potential after adjusting by Cox proportional hazards regression models (P < 0.05). CONCLUSIONS: Both B7-H1 and B7-1 are expressed in PC; these molecules are important markers for PC progression. Furthermore, combined B7-1/B7-H1 expression can serve as an independent prognostic marker for PC.