Common dysregulated genes and pathways in two sets of nasopharyngeal carcinoma biopsy samples from differential regions / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the common dysregulated genes and pathways shared by two sets of nasopharyngeal carcinoma (NPC) biopsy samples collected from different regions.</p><p><b>METHODS</b>Using bioinformatics analysis, the dysregulated genes and pathways in the two sets of samples were compared, and the relationship between the common dysregulated functions and genes was explored.</p><p><b>RESULTS</b>The common up-regulated genes in the two sets of samples were involved with such cell functions as cell cycle regulation, cell proliferation, DNA damage and repair, cell adhesion and migration, cell metabolism, and protein binding, but their common down-regulated genes did not show functional clustering. Those common dysregulated gene functions shown by differential gene expression profiling were not completely dictated by identical genes. The top 4 of the 10 common dysregulated pathways included leukocyte transendothelial migration, cell adhesion molecules, adherens junction, and phosphatidylinositol signaling system.</p><p><b>CONCLUSIONS</b>The differentially expressed genes in NPC are mainly related to cell cycle regulation, DNA damage and repair, cell adhesion and migration, a finding supporting the primary choice of chemotherapy in clinical treatment. The 4 most distinct common dysregulated pathways in the NPC samples are associated with tumor adhesion and migration, and by interventions of these pathways, especially the phosphatidylinositol signaling system in tumorigenesis, adhesion and migration, improvements in the therapeutic effect and prognosis of NPC can be expected.</p>

Screening and preliminary analysis of the apoptosis- and proliferation-related genes in nasopharyngeal carcinoma / 南方医科大学学报

<p><b>UNLABELLED</b>To screen and analyze the apoptosis- and proliferation-related genes in human nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>According to gene ontology classification, the abnormal expressions of the genes related to cell apoptosis and proliferation were identified in the NPC gene chip data. The cell apoptosis- and proliferation-related genes expressed in each of the 3 stages, as defined by the tree model for the pathogenesis and progression of NPC, were screened, and with literature review, their distribution in the tree model were analyzed.</p><p><b>RESULTS</b>Nineteen genes related to cell apoptosis were found in NPC, among which 9 were down-regulated (such as DNASE1L3) and located in the chromosome deletion regions, and 10 were up-regulated (such as DEDD) in the chromosome amplification regions. Twenty-one cell proliferation-related genes were identified, including 8 down-regulated genes (such as TUSC2) in the chromosome deletion regions and 13 up-regulated ones (such as EMP1) in the chromosome amplification regions. In the chromosome deletion regions, the down-regulated cell apoptosis-related genes participated mostly in inducing and regulating cell apoptosis, and the up-regulated cell proliferation-related genes in the chromosome amplification regions were mostly associated with the positive regulation of cell proliferation.</p><p><b>CONCLUSION</b>NPC occurs possibly through two pathways by inhibiting cell apoptosis or by promoting excessive cell proliferation.</p>

Establishment of a nude mouse model of nasopharyngeal carcinoma lymph node metastasis and screening of the metastasis-related signature genes / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a nude mouse model of nasopharyngeal carcinoma (NPC) lymph node metastasis and screen the signature genes associated with the metastasis.</p><p><b>METHODS</b>The NPC 5-8F-EGFP cells were inoculated into nude mice, from which a 5-8F-LN cell line with lymph node metastasis potential was obtained. The lymphatic metastasis-related signature genes of breast cancer and head and neck squamous cell carcinoma were screened by data mining method.</p><p><b>RESULTS</b>The NPC cell lines 5-8F and 6-10B showed 307 differentially expressed genes by microarray analysis, from which 20 overlapping genes were identified, and 3 overexpressed genes were found with probable metastasis potential, namely the ADM, IRF1, and CAV1 genes. Quantitative RT-PCR validated the data mining results in the 5-8F-EGFP, 6-10B-EGFP, NP69, and 5-8F-LN cell lines. The 3 NPC cell lines 5-8F-EGFP, 6-10B-EGFP and 5-8F-LN showed significantly higher expressions of IRF1 than NP69 cells (P=0.008, 0.022, and 0.006, respectively. The expression level of CAV1 in 5-8F-EGFP cells was significantly higher than that in 6-10B-EGFP cells (P=0.014), but ADM expression showed no significant difference between the 4 cell lines.</p><p><b>CONCLUSIONS</b>IRF1 may play an important role in the progression of NPC. The overexpression of CAV1 in 5-8F-EGFP cells can be associated with the high metastatic potential of the cells.</p>

Exploration of multigene, multistep and multipathway model of nasopharyngeal and colorectal carcinogenesis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To construct tree models for nasopharyngeal carcinoma (NPC)and explore the oncogenesis process of NPC.</p><p><b>METHODS</b>Based on the software which Desper et al developed, tree models were constructed for colorectal carcinoma (CC) from the comparative genomic hybridization (CGH) data of 118 CC patients and for NPC from the CGH data of 140 southern Chinese patients, respectively.</p><p><b>RESULTS</b>Tree models for CC suggested that changes in -18q and +20q were important early events in colorectal carcinogenesis. As changes in -18q occurred prior to those in -17p, there might be some cause-effect relationship. Tree models for NPC suggested that change in -3p was an important early event in nasopharyngeal carcinogenesis, and those in -11q, -14q, -16q, -9p were also non-random genetic events in carcinogenesis, suggesting that there might be tumor-associated genes existing on these chromosome arms. The tree model also suggested the existence of oncogene on the short arm of chromosome 12.</p><p><b>CONCLUSION</b>Constructing tree models based on the CGH data to demonstrate the initiation and progression of NPC might help elucidate its multigene, multistep and multipathway development. It may provide valuable clues to explore the mechanism of tumorigenesis.</p>