Early screening of nasopharyngeal carcinoma.

The low positive predictive value (PPV) of early screening of nasopharyngeal carcinoma (NPC) is the problems that need to be solved urgently. The combination of cell-free DNA (cfDNA) methylation testing and Epstein-Barr virus (EBV) serological testing is the key to solve this problem. This paper reviews recent advances in early screening for NPC and cfDNA methylation, with future perspectives. Pubmed was searched for the literature related to early screening of NPC and cfDNA methylation in the past 5 years. The results of these studies were summarized. Despite these efforts, the PPV is still low (10%). Previous studies have shown that cfDNA methylation analysis has good specificity and accuracy across a variety of tumors. The combination of cfDNA methylation and EBV detection helps to improve the PPV for early screening of NPC. The combination of cfDNA methylation and EBV serological testing is key to addressing the low PPV of NPC early screening.

Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis.

Increased vascular permeability facilitates metastasis. Cancer-secreted exosomes are emerging mediators of cancer-host crosstalk. Epstein-Barr virus (EBV), identified as the first human tumor-associated virus, plays a crucial role in metastatic tumors, especially in nasopharyngeal carcinoma (NPC). To date, whether and how exosomes from EBV-infected NPC cells affect vascular permeability remains unclear. Here, we show that exosomes from EBV-positive NPC cells, but not exosomes from EBV-negative NPC cells, destroy endothelial cell tight junction (TJ) proteins, which are natural barriers against metastasis, and promote endothelial-to-mesenchymal transition (EndMT) in endothelial cells. Proteomic analysis revealed that the level of HMGA2 protein was higher in exosomes derived from EBV-positive NPC cells compared with that in exosomes derived from EBV-negative NPC cells. Depletion of HMGA2 in exosomes derived from EBV-positive NPC cells attenuates endothelial cell dysfunction and tumor cell metastasis. In contrast, exosomes from HMGA2 overexpressing EBV-negative NPC cells promoted these processes. Furthermore, we showed that HMGA2 upregulates the expression of Snail, which contributes to TJ proteins reduction and EndMT in endothelial cells. Moreover, the level of HMGA2 in circulating exosomes is significantly higher in NPC patients with metastasis than in those without metastasis and healthy negative controls, and the level of HMGA2 in tumor cells is associated with TJ and EndMT protein expression in endothelial cells. Collectively, our findings suggest exosomal HMGA2 from EBV-positive NPC cells promotes tumor metastasis by targeting multiple endothelial TJ and promoting EndMT, which highlights secreted HMGA2 as a potential therapeutic target and a predictive marker for NPC metastasis.

Epstein-Barr Virus Induces Lymphangiogenesis and Lympth Node Metastasis via Upregulation of VEGF-C in Nasopharyngeal Carcinoma.

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common Epstein-Barr virus (EBV)-associated head and neck malignancy. However, the effect of EBV on NPC lymph node (LN) metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF1a hyperactivity and subsequent VEGF-C transcriptional activation. In addition, administration of anti-VEGF-C antibody or HIF1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF1a, and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis. IMPLICATIONS: This research demonstrates that EBV induces lymphangiogenesis in NPC by regulating PHLPP1/p-AKT/HIF1a/VEGF-C, providing a new therapeutic target for NPC with lymphatic metastasis.

GenCLiP 3: mining human genes' functions and regulatory networks from PubMed based on co-occurrences and natural language processing.

SUMMARY: We present a web server, GenCLiP 3, which is an updated version of GenCLiP 2.0 to enhance analysis of human gene functions and regulatory networks, with the following improvements: i) accurate recognition of molecular interactions with polarity and directionality from the entire PubMed database; ii) support for Boolean search to customize multiple-term search and to quickly retrieve function related genes; iii) strengthened association between gene and keyword by a new scoring method; and iv) daily updates following literature release at PubMed FTP. AVAILABILITY: The server is freely available for academic use at: http://ci.smu.edu.cn/genclip3/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

Prospective, single-center cohort study analyzing the efficacy of complete laparoscopic resection on recurrent hepatocellular carcinoma.

BACKGROUND: Laparoscopic hepatectomy is increasingly being used to treat hepatocellular carcinoma (HCC). However, few studies have examined the treatment of recurrent HCC in patients who received a prior hepatectomy. The present prospective study compared the clinical efficacy of laparoscopic surgery with conventional open surgery in HCC patients with postoperative tumor recurrence. METHODS: We conducted a prospective study of 64 patients, all of whom had undergone open surgery once before, who were diagnosed with recurrent HCC between June 2014 and November 2014. The laparoscopic group (n = 31) underwent laparoscopic hepatectomy, and the control group (n = 33) underwent conventional open surgery. Operation time, intraoperative blood loss, surgical margins, postoperative pain scores, postoperative time until the patient could walk, anal exsufflation time, length of hospital stay, and inpatient costs were compared between the two groups. The patients were followed up for 1 year after surgery, and relapse-free survival was compared between the two groups. RESULTS: All surgeries were successfully completed. No conversion to open surgery occurred in the laparoscopic group, and no serious postoperative complications occurred in either group. No significant difference in inpatient costs was found between the laparoscopic group and the control group (P = 0.079), but significant differences between the two groups were observed for operation time (116.7 ± 37.5 vs. 148.2 ± 46.7 min, P = 0.031), intraoperative blood loss (117.5 ± 35.5 vs. 265.9 ± 70.3 mL, P = 0.012), postoperative time until the patient could walk (1.6 ± 0.6 vs. 2.2 ± 0.8 days, P < 0.05), anal exsufflation time (2.1 ± 0.3 vs. 2.8 ± 0.7 days, P = 0.041), visual analogue scale pain score (P < 0.05), postoperative hepatic function (P < 0.05), and length of hospital stay (4.5 ± 1.3 vs. 6.0 ± 1.2 days, P = 0.014). During the 1-year postoperative follow-up period, 6 patients in each group had recurrent HCC on the side of the initial operation, but no significant difference between groups was observed in the recurrence rate or relapse-free survival. In the laparoscopic group, operation time, postoperative time until the patient could walk, anal exsufflation time, and inpatient costs were not different (P > 0.05) between the patients with contralateral HCC recurrence (n = 18) and those with ipsilateral HCC recurrence (n = 13). However, intraoperative blood loss was significantly less (97.7 ± 14.0 vs. 186.3 ± 125.6 mL, P = 0.012) and the hospital stay was significantly shorter (4.2 ± 0.7 vs. 6.1 ± 1.7 days, P = 0.021) for the patients with contralateral recurrence than for those with ipsilateral recurrence. CONCLUSIONS: For the patients who previously underwent conventional open surgical resection of HCC, complete laparoscopic resection was safe and effective for recurrent HCC and resulted in a shorter operation time, less intraoperative blood loss, and a faster postoperative recovery than conventional open surgery. Laparoscopic resection was especially advantageous for the patients with contralateral HCC recurrence.

Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma.

Cell division cycle 20 (CDC20) encodes a regulatory protein interacting with the anaphase-promoting complex/cyclosome (APC/C) in the cell cycle and plays important roles in tumorigenesis and progression of multiple tumors. The present study aimed to investigate the clinical significance of CDC20 in hepatocellular carcinoma (HCC) and the role of CDC20 in the progression of HCC. By bioinformatics analysis, CDC20 was found to be the major node in HCC molecular interaction networks. Quantitative PCR and western blot analyses were applied to examine CDC20 expression in 16 paired primary HCC tissues. Immunohistochemistry (IHC) was performed to examine CDC20 protein expression in 132 matched paraffin-embedded HCC tissues and to analyze the relationship between CDC20 staining and clinical characteristics. Small interfering RNA (siRNA) targeting CDC20 was synthesized and transfected into HepG2 cells to investigate the role of CDC20 in cell growth and the cell cycle. Results show that CDC20 expression was upregulated in HCC tissues compared to adjacent non-tumor liver tissues. In the 132 matched HCC tissues, high expression levels of CDC20 were detected in 68.18% HCC samples, and overexpression of CDC20 was positively correlated with gender (P=0.013), tumor differentiation (P=0.000), TNM stage (P=0.012), P53 and Ki-67 expression (P=0.023 and P=0.007, respectively). Cells transfected with CDC20 siRNA showed a decrease in cell proliferation and increase in the number of cells in G2/M-phase. In conclusion, increased expression of CDC20 was demonstrated to be associated with the development and progression of HCC, and may be regarded as a promising therapeutic target for HCC.

GenCLiP 2.0: a web server for functional clustering of genes and construction of molecular networks based on free terms.

UNLABELLED: Identifying biological functions and molecular networks in a gene list and how the genes may relate to various topics is of considerable value to biomedical researchers. Here, we present a web-based text-mining server, GenCLiP 2.0, which can analyze human genes with enriched keywords and molecular interactions. Compared with other similar tools, GenCLiP 2.0 offers two unique features: (i) analysis of gene functions with free terms (i.e. any terms in the literature) generated by literature mining or provided by the user and (ii) accurate identification and integration of comprehensive molecular interactions from Medline abstracts, to construct molecular networks and subnetworks related to the free terms. AVAILABILITY AND IMPLEMENTATION: http://ci.smu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Common dysregulated genes and pathways in two sets of nasopharyngeal carcinoma biopsy samples from differential regions].

OBJECTIVE: To explore the common dysregulated genes and pathways shared by two sets of nasopharyngeal carcinoma (NPC) biopsy samples collected from different regions. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Microarray analysis of differentially expressed genes between nasopharyngeal carcinoma cell lines 5-8F and 6-10B.

Nasopharyngeal carcinoma (NPC) cell lines 5-8F (high tumorigenic and metastatic) and 6-10B (low tumorigenic and metastatic) are subclones of SUNE1. To address their biological differences, three biologic repeats of expression microarray analysis were performed. Only 60 differently expressed genes were identified between the two cell lines. These genes were randomly distributed on all the chromosomes. Gene ontology analysis showed that most of these genes participated in cellular and metabolic processes, and the primary molecular functions of each were catalytic activity, ion binding, and protein binding. Literature mining revealed that these genes were specifically related to apoptosis, cell cycle, metastasis, chemokines, and immunoediting, but not cancer, NPC, stem cells, lymphangiogenesis, angiogenesis, inflammation, nor proliferation. In particular, 42/60 genes have established metastatic functions (P < 0.00001), while 11 out of those 42 genes formed gene networks related to metastasis (P = 0.013). Thus, the 60 genes identified by this microarray experiment most likely represent a core set of genes that comprise shared metastatic gene networks between the two cell lines and mediate their differential metastatic characteristics. Among the gene networks identified, the PTHLH gene was of particular interest. Predicted to regulate the WNT pathway through the DKK1 gene, the PTHLH gene may affect metastasis and apoptosis of NPC and merits further study.

[Screening and preliminary analysis of the apoptosis- and proliferation-related genes in nasopharyngeal carcinoma].

UNLABELLED: To screen and analyze the apoptosis- and proliferation-related genes in human nasopharyngeal carcinoma (NPC). METHODS: 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. RESULTS: 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. CONCLUSION: NPC occurs possibly through two pathways by inhibiting cell apoptosis or by promoting excessive cell proliferation.

Differential expression profiles of microRNAs in NIH3T3 cells in response to UVB irradiation.

MicroRNAs (miRNAs) are known as a kind of small, noncoding RNA, which play an important role in mediating many biological processes such as development, cell proliferation and differentiation in plants and animals. Here we report the differential expression profiles of miRNAs and characterized putative target genes in NIH3T3 cells at a series of different time points after UVB irradiation (compared with no UVB irradiation). The relative expression of mature miRNA genes was determined by miRNA microarray technique and the results were confirmed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Potential target genes of these miRNAs were classified into different function categories with the GOstat software (http://gostat.wehi.edu.au/cgi-bin/goStat.pl). Several miRNAs in this study expressed highly at different time points, especially mmu-miR-365 and mmu-miR-21. Three miRNAs were lowly expressed, of which mmu-miR-465 showed low levels of expression at all time points, whereas after 50 J m(-2) UVB irradiation mmu-miR-296 and mmu-miR-376c showed low levels of expression at 6 and 12 h, respectively. Our study provided a basis for the global characterization of UV-regulated miRNA expression.

[Establishment of a nude mouse model of nasopharyngeal carcinoma lymph node metastasis and screening of the metastasis-related signature genes].

OBJECTIVE: To establish a nude mouse model of nasopharyngeal carcinoma (NPC) lymph node metastasis and screen the signature genes associated with the metastasis. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

GenCLiP: a software program for clustering gene lists by literature profiling and constructing gene co-occurrence networks related to custom keywords.

BACKGROUND: Biomedical researchers often want to explore pathogenesis and pathways regulated by abnormally expressed genes, such as those identified by microarray analyses. Literature mining is an important way to assist in this task. Many literature mining tools are now available. However, few of them allows the user to make manual adjustments to zero in on what he/she wants to know in particular. RESULTS: We present our software program, GenCLiP (Gene Cluster with Literature Profiles), which is based on the methods presented by Chaussabel and Sher (Genome Biol 2002, 3(10):RESEARCH0055) that search gene lists to identify functional clusters of genes based on up-to-date literature profiling. Four features were added to this previously described method: the ability to 1) manually curate keywords extracted from the literature, 2) search genes and gene co-occurrence networks related to custom keywords, 3) compare analyzed gene results with negative and positive controls generated by GenCLiP, and 4) calculate probabilities that the resulting genes and gene networks are randomly related. In this paper, we show with a set of differentially expressed genes between keloids and normal control, how implementation of functions in GenCLiP successfully identified keywords related to the pathogenesis of keloids and unknown gene pathways involved in the pathogenesis of keloids. CONCLUSION: With regard to the identification of disease-susceptibility genes, GenCLiP allows one to quickly acquire a primary pathogenesis profile and identify pathways involving abnormally expressed genes not previously associated with the disease.

[Association of the coding region single nucleotide polymorphisms in PLUNC gene with nasopharyngeal carcinoma].

OBJECTIVE: To investigate whether the single nucleotide polymorphism (SNP) site G14595T of PLUNC gene coding region is significantly correlated with nasopharyngeal carcinoma (NPC). METHODS: Peripheral blood samples were collected from 239 NPC patients, 163 males and 76 females, aged 46.9, and 286 sex(-), and age(-)-matched healthy controls in Guangdong, China. The coding region and regulating region, 3'UTR and 3'Flank as well as 5'UTR and 5'Flank were sequenced to identify and characterize the SNPs. All SNP were analyzed by linkage disequilibrium (LD) and haplotype tag SNP (htSNP) derived from the results by calculating haplotype. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to study the PLUNC genotypes. RESULTS: Nine SNPs were obtained by sequencing. Eight of the 9 SNPs presented high LD, and 3 of the SNP were determined as htSNPs. The frequencies of genotype and allele on SNP marker G14595T in the NPC patients and controls suggested there was no significant association between the phenotype and NPC susceptibility (P > 0.05). CONCLUSION: The marker G14595T in coding region does not influence the expression of PLUNC gene. There is no significant association between the phenotype and susceptibility to NPC in Guangdong.

Construction and analysis of tree models for chromosomal classification of diffuse large B-cell lymphomas.

AIM: To construct tree models for classification of diffuse large B-cell lymphomas (DLBCL) by chromosome copy numbers, to compare them with cDNA microarray classification, and to explore models of multi-gene, multi-step and multi-pathway processes of DLBCL tumorigenesis. METHODS: Maximum-weight branching and distance-based models were constructed based on the comparative genomic hybridization (CGH) data of 123 DLBCL samples using the established methods and software of Desper et al. A maximum likelihood tree model was also used to analyze the data. By comparing with the results reported in literature, values of tree models in the classification of DLBCL were elucidated. RESULTS: Both the branching and the distance-based trees classified DLBCL into three groups. We combined the classification methods of the two models and classified DLBCL into three categories according to their characteristics. The first group was marked by +Xq, +Xp, -17p and +13q; the second group by +3q, +18q and +18p; and the third group was marked by -6q and +6p. This chromosomal classification was consistent with cDNA classification. It indicated that -6q and +3q were two main events in the tumorigenesis of lymphoma. CONCLUSION: Tree models of lymphoma established from CGH data can be used in the classification of DLBCL. These models can suggest multi-gene, multi-step and multi-pathway processes of tumorigenesis. Two pathways, -6q preceding +6q and +3q preceding +18q, may be important in understanding tumorigenesis of DLBCL. The pathway, -6q preceding +6q, may have a close relationship with the tumorigenesis of non-GCB DLBCL.

Reexploring the possible roles of some genes associated with nasopharyngeal carcinoma using microarray-based detection.

In gene expression profiling, nasopharyngeal carcinoma (NPC) 5-8F cells differ from 6-10B cells in terms of their high tumorigenicity and metastatic ability. Differentially expressed genes from the two cell types were analyzed by combining with MILANO (the automatic custom annotation of microarray results which is based on all the available published work in PubMed). The results showed that five genes, including CTSD, P63, CSE1L, BPAG1 and EGR1, have been studied or mentioned in published work on NPC. Subsequently, we reevaluated the roles of these genes in the pathogenesis of NPC by combining the data of gene chips from NPCs versus NPs and pooled cells from 5-8F, 6-10B and CNE2 versus NPs. The results suggested that the roles of BPAG1 and EGR1 are possibly different from those reported in previous NPC studies. These five genes are likely to be involved in the proliferation, apoptosis, invasion and metastasis of NPC. A reexploration of the genes will further define their roles in the pathogenesis of NPC.

[Predicting human tumor-specific promoter using transcription factor binding sites].

To predict human tumor-specific promoters using computer technology, three data sets of tumor-specific promoter sequences, transcription factor binding site sequences and non-tumor promoter sequences were collected, and the tumor-specific promoter sequences and non-tumor promoter sequences were analyzed for the comparative density of each unique transcription factor binding site. The density of each transcription factor binding site in the corresponding data set was used to derive the density ratio, from which the eigenvector was constructed to identify human tumor-specific promoters. This method proved to be highly accurate in predicting the tumor-specific promoters, with recognition rates of over 90% of the training sequences and over 80% of the testing sequences.

[Mining gene expression microarray data of nasopharyngeal carcinoma by literature profiling].

OBJECTIVE: To study abnormal signal pathway in nasopharyngeal carcinoma (NPC). METHOD: NPC gene expression microarray data was mined by analysis of literature profiles generated by extracting the frequencies of certain terms from the abstracts stored in the Medline literature database. The terms were then filtered on the basis of both repetitive occurrence and co-occurrence among multiple gene entries. Finally, clustering analysis was performed on the retained frequency values, shaping a coherent picture of the functional relationship among large and heterogeneous lists of genes. RESULT: Sixteen function groups were found among 112 abnormally expressed genes, including 4 groups indicative of Epstein-Barr virus (EBV) infection, 6 groups indicative of normal nasopharyngeal tissues that acquired essential capabilities to develop into tumor, 2 groups involved in energy metabolism, 1 group suggesting abnormal phosphorylation of proteins, 2 groups related to other diseases, and 1 group associated with muscle activities. The pathways of p53 and Rb, which were frequently abnormal during tumor progression, were not found in these groups. CONCLUSION: Initiation and progression of NPC may be caused by special signal transduction pathways.

[Exploration of multigene, multistep and multipathway model of nasopharyngeal and colorectal carcinogenesis].

OBJECTIVE: To construct tree models for nasopharyngeal carcinoma (NPC)and explore the oncogenesis process of NPC. METHODS: 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. RESULTS: 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. CONCLUSION: 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.