Effect of exosomes derived from human Epstein-Barr virus-positive nasopharyngeal carcinoma cells on lymphangiogenesis and lymph node metastasis / 南方医科大学学报

OBJECTIVE@#To investigate the effect of exosomes derived from Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) cells on lymphangiogenesis and lymph node metastasis of NPC.@*METHODS@#Exosomes from NP69 cells and EBV-positive HK1 (HK1-EBV) cells were obtained by ultracentrifugation and identified by Western blotting and nanoparticle tracking analysis. Dio dye phagocytosis test was performed to observe exosome uptake by lymphatic endothelial cells. Lymphatic endothelial cells were treated with exosomes from nasopharyngeal epithelium (NP69), HK1-EBV, and C666-1 cells or exosome-free supernatant of HK1-EBV and C666-1 cells, and tube formation and migration of the cells were observed. In a nude mouse model of popliteal lymph node metastasis of NPC, the effects of normal saline, NP69 cell-derived exosomes, HK1-EBV cell-derived exosomes, exosome-free supernatant of HK1-EBV cells, and HK1-EBV exosome-free supernatant protein on lymphangiogenesis and lymph node metastasis of the tumor were observed.@*RESULTS@#The exosomes obtained by ultracentrifugation contained abundant exosome-specific proteins and showed a normal size range. The exosomes from NPC cells and NP69 cells could be taken up by lymphatic endothelial cells. Compared with the blank control and exosomes form NP69 cells, exosomes derived from HK1-EBV and C666-1 cells significantly promoted tube formation and migration of lymphatic endothelial cells (@*CONCLUSIONS@#Exosomes from EBV-positive NPC cells can significantly promote lymphangiogenesis and lymph node metastasis of NPC.

Differentially expressed genes and potential signaling pathway in Asian people with breast cancer by preliminary analysis of a large sample of the microarray data / 南方医科大学学报

<p><b>OBJECTIVE</b>To screen differentially expressed genes and identify potential signaling pathway in Asian people with breast cancer.</p><p><b>METHODS</b>Five gene microarray datasets of Asian people with breast cancer, GSE6367, GSE9309, GSE15852, GSE33447 and GSE45255, were downloaded from GEO. Microarrays with 318 breast cancer and 60 normal breast tissues were used for analysis of differentially expressed genes and pathway. 32 pairs of breast cancer patients' specimens were used to validate the differentially expressed genes by real-time PCR.</p><p><b>RESULTS</b>Analysis of the large sample of microarray data identified 436 differentially expressed genes in breast cancer tissues, while 259 of these genes were up-regulated and the other 177 down-regulated. Pathway analysis showed that metabolism-related signaling pathway may be involved in the development of breast cancer in Asian people. The expressions of KRT19, ADIPOQ, CFD, RBP4, LPL, ABCA8 and CD36 genes were confirmed by real-time PCR.</p><p><b>CONCLUSION</b>This study shows differential gene expression profile and potential signaling pathway in Asian people with breast cancer. CD36 gene may be closely related to the Asian breast cancer. ABCA8 gene may be a new disease gene in Asian breast cancer.</p>

Differential gene expression profiling for identification of protective transcription factors in different subtypes of nasopharyngeal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the dysregulated genes among the differentially expressed genes in 41 nasopharyngeal biopsy samples and identify their protective transcriptional factors.</p><p><b>METHODS</b>The differentially expressed gene profiles were obtained by analyzing both types I and II nasopharyngeal carcinoma (NPC_I and NPC_II, respectively) using EXCEL and Bioinformatics tools. The transcriptional factors were further studied only when (1) the difference in the binding sites of the differentially expressed genes between NPC_I and NPC_II groups was statistically significant, (2) the expressions of the transcription factors were correlated with the gene expressions in the samples, and (3) the transcription factors affected at least 40% of the expression of the related genes.</p><p><b>RESULTS</b>In NPC_I samples, 80 transcription factors were found to be up-regulated, in which RUNX3, GATA3, NR3C1, NRF1, RXRA, SMAD7, TBP, and ZBTB6 were positive factors and HLF and MTF1 were negative factors, involved in the regulation of the genes in T cell receptor signaling pathway. No eligible transcription factors were found in association with down-regulated genes in NPC_I compared to NPC_II gene expression profiles.</p><p><b>CONCLUSIONS</b>The over-expressed genes in NPC_I are mainly related to immune responses, and we found 8 positive factors and 2 negative factors that regulate the genes in T cell receptor signaling pathway. The 10 transcription factors may serve as potential therapeutic targets for NPC_I. We failed to identify any transcription factors associated with down-regulated genes in NPC_I relative to NPC_II possibly as a result of multiple factors that affect the differential gene expressions in NPC_II including the transcription factors, DNA phosphorylation and modification, chromosome variation and environmental factors.</p>

Analysis of angiogenesis and lymphangiogenesis signaling pathways based on gene expression patterns of nasopharyngeal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To pinpoint angiogenesis- and lymphangiogenesis-related genes in nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Based on the reported microarray data which identified 831 differentially expressed genes in NPC tissues and the latest genomic information, we selected 246 genes for analysis with the smallest differential expression threshold of 260. Gene function analysis and network construction was carried out based on literature mining for analysis of the signaling pathways related with angiogenesis and lymphangiogenesis of NPC.</p><p><b>RESULTS</b>The 246 genes were related with such keywords as nasopharyngeal carcinoma, EB virus, metastasis, angiogenesis, lymphangiogenesis, and invasion. Particularly, we found that up to 52 genes were associated with angiogenesis (P=0.00001), and 19 genes form 12 related gene pairs (P=0.0042). Twenty-one lymphangiogenesis-related genes were identified (P=0.00001), and 6 of these genes formed a gene network (P=0.0226). Eight genes, including PTGS2, participated in the nuclear factor-κB (NF-κB) pathway, which was closely related to angiogenesis in small cell lung cancer (P=7.87E-07). Five genes, including STAT1 and CXCL10, participated in toll-like receptor signaling pathway (P=0.00176).</p><p><b>CONCLUSION</b>PTGS2 and NF-κB promote angiogenesis of NPC, and the role of toll-like receptor signaling pathway in lymphangiogenesis warrants further investigation.</p>

Construction of evolutionary tree model for esophageal carcinogenesis based on comparative genome hybridization data / 中国病理生理杂志

AIM:Based on comparative genomic hybridization(CGH) data,to construct tree model of esophageal carcinoma and to explore mechanism of multigene involved,multistep development and multipathway progression during esophageal carcinogenesis.METHODS:Using the software developed by Desper et al,tree models of esophageal carcinoma were constructed according to the CGH data of 78 esophageal carcinoma patients.RESULTS:Tree models for esophageal carcinoma suggested that there were-4p,-9p,-18q,+7p,+8q,+17p,+17q,+20p,+20q nine nonrandom genetic events,and +7p、+8q and +20q might be important early events in esophageal carcinogenesis,indicating that there might be cancer-related genes in these chromosomal arms.CONCLUSION:Tree models based on CGH data of esophageal carcinoma imply the process of multigene involved,multistep and multipathway progression.The tree models also give the direction to search for esophageal cancer-related genes.