Enhanced expression of cohesin loading factor NIPBL confers poor prognosis and chemotherapy resistance in non-small cell lung cancer.

BACKGROUND: NIPBL, the sister chromatid cohesion 2 (SCC2) human homolog, is a cohesin loading factor which is essential for deposition of cohesin onto the sister chromatid. Recent studies have shown that NIPBL contribute to sister chromatid cohesion and plays a critical role in development, DNA repair, and gene regulation. In this study, we measured the expression of NIPBL in clinical non-small cell lung cancer specimens, and determined its effects on cellular processes and chemosensitivity in vitro. METHODS: NIPBL immunohistochemistry was performed on 123 lung adenocarcinoma samples. Through knockdown of NIPBL protein expression, non-small cell lung cancer cell lines were used to test the potential involvement of NIPBL silencing on cell proliferation, migration, invasion, and apoptosis. Chemosensitivity was assessed with clonogenic assays, and chromatin immunoprecipitation assays were performed to analyze the relationship between NIPBL and signal transducers and activators of transcription 3 (STAT3). RESULTS: Immunohistochemical analysis showed that high expression of NIPBL was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis further indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer. Knockdown of NIPBL in non-small cell lung cancer cell lines significantly reduced cellular proliferation, migration, and invasion, and enhanced cellular apoptosis and sensitivity to cisplatin, paclitaxel, and gemcitabine hydrochloride. NIPBL bound to the promoter region of the STAT3 gene, directly regulating the expression of STAT3. CONCLUSIONS: These data suggested that NIPBL played a significant role in lung carcinogenesis. NIPBL expression conferred poor prognosis and resistance to chemotherapy in non-small cell lung cancer, suggesting that NIPBL may be a novel therapeutic target.

Down Expression of FBP1 Is a Negative Prognostic Factor for Non-Small-Cell Lung Cancer.

Downregulation of fructose-1,6-bisphosphatse-1 (FBP1) was observed in several cancers but its role in the lung cancer still remains unknown. We examined the cancer tissues from 140 patients with nonsmall cell lung cancer patients and found that the relative gene expression of FBP1 was significantly lower in lung cancer tissues as compared to incisal marginal tissues and normal tissues. The patients with higher level of FBP1 RNA expression have significantly longer disease free survival and overall survival as compared to the lower expression groups. There was a negative correlation with the level of FBP1 and recurrence of the lung cancer.

Establishment and Characterization of a CD20-Positive NK/T-Cell Lymphoma Cell Line.

BACKGROUND: CD20 positive NK/T-cell lymphoma is extremely rare and difficult for clinical treatment. Due to the lack of an established cell model for this disease, less is known about its biological characterization and potential therapeutic options. METHODS: A cell line of NK/T-cell lymphoma, which was enriched by magnetic sorting with proper cell surface markers (CD56) from peripheral blood mononuclear cells (PBMCs) drawn from a 21-year-old male patient with nasal angiocentric NK/T-cell lymphoma, was designated as ZQNK-29. Immunophenotypic analysis of ZQNK-29 was performed by flow cytometric and immunohistochemical analysis. Comparative genomic hybridization (CGH) analysis was used for cytogenetic analysis of ZQNK-29. Potential rearrangements of the immunoglobulin gene and Epstein-Barr virus (EBV) infection were examined by PCR and RT-PCR, respectively. RESULTS: ZQNK-29 cells express the phenotypic T-cell marker (CD3), T cell activation markers (HLA-DR), markers for both NK and cytotoxic T lymphocytes (TIA-1), and B-lineage marker CD20; however, expression of CD56 was not detected in expanded ZQNK-29 cells although this NK cell surface marker was used as one of selective cell surface markers for the initial isolation of NK/T cells. RT-PCR analysis showed that the pattern of gene expressions for infected EBV was latency type III, with the expressions of LMP1, EBNA-1, and EBNA-2; no rearrangements were found in the heavy-chain of the immunoglobulin gene or in the y chain of the T cell receptors (TCRs) gene. CGH analysis demonstrated that ZQNK-29 possessed an abnormal karyotype, 46XY, 1p (dist)+, 4p (dist)+, 4q (mid)-, 5q (mid)-, 9q (dist)+, 16p (dist)+, 16q (dist)+, 17p+, 17q (dist)+, 19q (dist)+, 20p+, 20q+, 21q+, and 22q+. Of these, 1p (dist)+, which has been confirmed to be mitochondrial DNA amplification, is believed to be mainly caused by EBV infection. CONCLUSIONS: ZQNK-29 is a well characterized premature human NK/T-cell lymphoma cell line with expression of the B-cell marker CD20 and will provide a useful pre-clinic model for characterization and potential therapeutic studies of the aggressive NK/T-cell lymphoma.

[Clinicopathologic and prognostic significance of serum levels of cytokines in patients with advanced serous ovarian cancer prior to surgery].

OBJECTIVE: To study the clinicopathologic and prognostic significance of serum levels of six cytokines (IFN-γ, TNF-α, IL-10, IL-5, IL-4, IL-2) in patients with advanced serous ovarian cancer prior to surgery. METHODS: The serum levels of six cytokines were detected in 51 patients with advanced serous ovarian cancer and 46 healthy controls, using cytometric bead arrays. RESULTS: The serum levels of IFN-γ (20.68±11.45), IL-2 (4.54±1.18), IL-4 (5.66±2.25), IL-5 (2.72±0.86) µg/L and IL-10 (5.93±7.92) µg/L were higher (P<0.01, P<0.05) and the serum level of TNF-α (7.53±8.47) was lower (P<0.01) in patients with advanced serous ovarian cancer than those in the healthy controls. The IFN-γ/IL-4 ratio (3.93±2.34) of the patients was lower than that of the controls (P<0.01). Kaplan-Meier analysis revealed that patient's age (P=0.016), menopausal status (P=0.001) and serum IL-10 level (P=0.010) correlated significantly with patient's survival. Cox regression analysis showed that serum IL-2 (P=0.045) and IL-10 levels (P=0.007) were the independent prognostic factors. CONCLUSIONS: Patients with advanced serous ovarian cancer have Th1/Th2 imbalance and immune function disturbance. The age of patients and menopausal status are important prognostic factors. IL-2 and IL-10 level are also independent predictors of survival.

[Study of the metastasis-associated genes and its copy numbers variation in highly metastatic epithelial ovarian cancer].

OBJECTIVE: To investigate the relationship of the metastasis-associated genes and its copy numbers variation in the highly metastatic human epithelial ovarian cancer cell line HO-8910PM. METHODS: The differentially expressed genes and its copy number variation between HO-8910PM cell line and normal ovarian tissues was detected by human genome U133A 2.0 gene chip and human mapping 10K array 2.0 gene chip, and the data was analyzed by bioinformatics. Some of metastasis-associated genes were validated the results of single nucleotide polymorphism (SNP) and cDNA chips by fluorescence in situ hybridization (FISH) and real-time quantitative PCR. RESULTS: Integrate analysis of two gene chips data showed that there were 385 differentially expressed genes in the same and 379 SNP positional point (6 of them, included 2 genes) between HO-8910PM cell line and normal ovarian tissues, these copy number amplification of 379 SNP positional point of chromosome were > or = 3, which had 240, deletion < or = 1 had 139. Chromosome location analysis showed that there were 385 differentially expressed genes located at all chromosomes, and 261 of them (67.8%, 261/385) located at 10 chromosomes, included that 34 (8.8%), 33 (8.6%), 28 (7.3%), 27 (7.0%), 25 (6.5%), 24 (6.2%) of them located at chromosome 3, 2, 9, 10, 1 and 11 respectively, and 23 (6.0%) of them at chromosome 6 and 12 each, 22 (5.7%) of them at chromosome 4 and 5 each. For the function of differentially expressed genes, the results showed that 99 (25.7%) genes belonged to the family of enzymes and their regulators, 54 (14.0%) genes associated with signal transduction, 50 (13.0%) genes associated with nucleic acid binding, and 36 (9.4%) genes associated with protein binding. CONCLUSION: We have demonstrated that there are 4 kinds of differentially expressed genes related to metastasis of ovarian cancer, which belonged to the families enzyme and its regulator, nucleic acid binding, signal transduction and protein binding, and located at chromosome 1, 2, 3, 4, 5, 6, 9, 10, 11 and 12.

Prognostic role of multidrug resistance-associated protein 1 expression and platelet count in operable non-small cell lung cancer.

The overall survival rate of patients with non-small cell lung cancer (NSCLC) following resection remains poor due to the high rates of recurrence and metastasis. The investigation of novel biomarkers is clinically necessary to improve treatment strategies. Multidrug resistance-associated protein 1 (MRP1) and platelet count are linked to a poor prognosis in various types of cancer. However, it is unknown whether MRP1 or platelet count is a suitable prognostic indicator of NSCLC. In the present study, 427 patients with operable NSCLC were enlisted. The association of MRP1 expression and platelet count with clinical pathological factors and patient outcome was evaluated. MRP1 expression was found to be significantly associated with sex, histological type and tumor differentiation, while platelet count was significantly associated with smoking behavior, histological type and clinical stage. Platelet count was significantly higher in patients with negative MRP1 expression than in those with positive MRP1 expression. Survival analysis indicated that there was no association between MRP1 expression and disease-free survival (DFS) or overall survival (OS) time. In the patients with no lymph node metastasis, the OS time was significantly longer in patients with positive MRP1 expression than in those with negative expression. However, in the patients with lymph node metastasis, the DFS time was significantly shorter in patients with positive MRP1 expression than in those with negative expression. There was an association between the platelet count and DFS and OS times, which were significantly longer in patients with a normal platelet count than in those with thrombocytosis. In conclusion, MRP1 expression and platelet count are valuable independent prognostic biomarkers for survival in operable NSCLC.

Identification of differentially expressed genes in the high and low metastatic human ovarian cancer cell lines and analyses of their chromosomal localizations and functions.

Oligonucleotide microarrays were used to study the differences of gene expressions in high (H) and low (L) metastatic ovarian cancer cell lines and in normal ovarian tissues (C). Bioinformatics was used to identify novel genes and their functions as well as chromosomal localizations. A total of 409 genes were differentially expressed between the high and low metastatic ovarian cancer cell lines. Of them, 271 genes were up regulated (Signal Log Ratio[SLR] > or = 1), and 138 genes were down regulated (SLR < or = -1). Except one gene whose location was unknown, all these genes were localized randomly on all the chromosomes, with a majority of them localized to Chromosomes 1, 6, 2, 17, 3, 5 and 11. Chromosome 1 contained, 43 of them (10.7%), the most for a single chromosome. A total of 264 genes (64.7%) were localized on the short arm of the chromosome (q). Functional classification showed that the 104 (25.4%) genes coding for enzymes and enzyme regulators made up the largest functional group, followed by signal transduction activity genes (43, 10.5%), nucleic acid binding activity genes (42, 10.3%), and proteins binding activity genes (34, 8.3%). These four groups accounted for 54.5% of all the differentially expressed genes. In addition, the functions of 76 genes (18.6%) were unknown. Tumor metastasis is the result of a number of genes acting in concert. The four functional groups of genes classified among these genes and their abnormalities would be the focus of further studies on ovarian cancer metastasis.

Function and chromosome location of differentially expressed genes in gastric cancer.

Using Affymetrix U133A oligonucleotide microarrays, screening was done for genes that were differentially expressed in gastric cancer (T) and normal gastric mucosa (C), and their chromosome location was characterized by bioinformatics. A total of 270 genes were found to have a difference in expression levels of more than eight times. Of them 157 were up-regulated (Signal Log Ratio [SLR] > or = 3), and 113 were down-regulated (SLR< or = -3). Except for, four genes with unknown localization, a vast majority of the genes were sporadically distributed over every chromosome. However, chromosome 1 contained the most differentially expressed genes (26 genes, or 9.8%), followed by chromosomes 11 and 19 (both 24 genes, or 9.1%). These genes were also more likely to be on the short-arm of the chromosome (q), which had 173 (65%). When these genes were classified according to their functions, it was found that most (67 genes, 24.8%) belonged to the enzymes and their regulators groups. The next group was the signal transduction genes group (43 genes, 15.9%). The rest of the top three groups were nucleic acid binding genes (17, 6.3%), transporter genes (15, 5.5%), and protein binding genes (12, 4.4%). These made up 56.9% of all the differentially expressed genes. There were also 50 genes of unknown function (18.5%). Therefore it was concluded that differentially expressed genes in gastric cancer seemed to be sporadically distributed across the genome, but most were found on chromosomes 1, 11 and 19. The five groups associated genes abnormality were important genes for further study on gastric cancer.

Correlation of neuroendocrine features with prognosis of non-small cell lung cancer.

The improvement in histological diagnostic tools, including neuroendocrine markers by immunohistochemistry (IHC), has led to increased recognition of non-small cell lung cancer (NSCLC) with neuroendocrine (NE) feature. However, little is known regarding the prevalence and clinical implications of NE feature in patients with NSCLC. In this study, we performed IHC in a tissue microarray containing 451 Chinese NSCLC cases, and analyzed correlation of the expression of neuroendocrine marker with pathological and clinical features of NSCLC. The result showed that NE feature in NSCLC was detectable in almost 30% of studied patients, and tumors with NE feature were significantly correlated with pathological classification, clinical stages and cell differentiation of NSCLC. Our data also revealed that NE feature indicated worse overall survival and disease free survival. Compared with mutant p53, NE markers showed more significance as for prognostic evaluation. Multi-factor COX analysis further suggested a potential clinical impact for NE feature as an independent indicator of poor prognosis for NSCLC patients.

Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip.

AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results. RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes, 530 were up-regulated (Signal Log Ratio (SLR) >2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64 genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35 were down-regulated (SLR<-2). CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.

Difference of gene expression profiles between esophageal carcinoma and its pericancerous epithelium by gene chip.

AIM: To study the difference of gene expression between esophageal carcinoma and its pericancerous epithelium and to screen novel associated genes in the early stage of esophageal carcinogenesis by cDNA microarray. METHODS: Total RNA was extracted with the original single step way from esophageal carcinoma, its pericancerous epithelial tissue and normal esophageal epithelium far from the tumor. The cDNA retro-transcribed from equal quantity of mRNA was labeled with Cy5 and Cy3 fluorescence functioning as probes. The mixed probes were hybridized with two pieces of BioDoor 4 096 double dot human whole gene chip. Fluorescence signals were scanned by ScanArray 3 000 laser scanner and farther analyzed by ImaGene 3.0 software with the digital computer. RESULTS: (1) A total of 135 genes were screened out, in which 85 and 50 genes whose the gene expression levels (fluorescence intensity) in esophageal carcinoma were more than 2 times and less than 0.5 times respectively compared with the normal esophageal epithelium. (2) There were also total 31 genes, among then 27 and 4 whose expressions in pericancerous tissue were 2-fold up-regulated and 0.5-fold down-regulated respectively compared with normal esophageal epithelium. (3) There were 13 genes appeared simultaneously in both pericancerous epithelium and esophageal carcinoma, while another 18 genes existed in pericancerous epithelium only. CONCLUSION: With the parallel comparison among these three gene profiles, it was shown that (1). A total of 135 genes, Whose expression difference manifested as fluorescence intensity were more than 2 times between esophageal carcinoma and normal esophageal epithelium, were probably related to the occurrence and development of the esophageal carcinoma. (2). The 31 genes showing expression difference more than 2 times between pericancerous and normal esophageal epithelium might be relate to the promotion of esophageal pericancerosis and its progress. The present study illustrated that by using the gene chip to detect the difference of gene expression profiles might be of benefit to the gene diagnosis, treatment and prevention of esophageal carcinoma.

Gene expression profile differences in high and low metastatic human ovarian cancer cell lines by gene chip.

OBJECTIVES: To study the difference between gene expressions of high (H0-8910PM) and low (HO-8910) metastatic human ovarian carcinoma cell lines and screen novel associated genes by cDNA microarray. METHODS: cDNA retro-transcribed from equal quantities of mRNA derived from high and low metastatic tumor cells or normal ovarian tissues were labeled with Cy5 and Cy3 fluorescein as probes. The mixed probe was hybridized with two pieces of BioDoor 4096 double dot human whole gene chip and scanned with a ScanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. RESULTS: A total of 355 genes with expression levels more than 3 times larger were found by comparing the HO-8910 cell with normal ovarian epithelial cells. A total of 323 genes with expression levels more than 3 times larger in HO-8910PM cells compared to normal ovarian epithelium cells were also detected. A total of 165 genes whose expression levels were more than two times those of HO-8910PM cells compared to their mother cell line (HO-8910) were detected. Twenty-one genes with expression levels > 3 times were found from comparison of these two tumor cell lines. CONCLUSIONS: cDNA microarray techniques are effective in screening differential gene expression between two human ovarian cancer cell lines (H0-8910PM; HO-8910) and normal ovarian epithelial cells. These genes may be related to the genesis and development of ovarian carcinoma. Analysis of the human ovarian cancer gene expression profile with cDNA microarray may help in gene diagnosis, treatment and prevention.

Effect of adjuvant magnetic fields in radiotherapy on non-small-cell lung cancer cells in vitro.

OBJECTIVES: To explore sensitization and possible mechanisms of adjuvant magnetic fields (MFs) in radiotherapy (RT) of non-small-cell lung cancer. METHODS: Human A549 lung adenocarcinoma cells were treated with MF, RT, and combined MF-RT. Colony-forming efficiency was calculated, cell cycle and apoptosis were measured, and changes in cell cycle- and apoptosis-related gene expression were measured by microarray. RESULTS: A 0.5 T, 8 Hz stationary MF showed a duration-dependent inhibitory effect lasting for 1-4 hours. The MF-treated groups had significantly greater cell inhibition than did controls (P < 0.05). Surviving fractions and growth curves derived from colony-forming assay showed that the MF-only, RT-only, and MF-RT groups had inhibited cell growth; the MF-RT group showed a synergetic effect. Microarray of A549 cells exposed for 1 hour to MF showed that 19 cell cycle- and apoptosis-related genes had 2-fold upregulation and 40 genes had 2-fold downregulation. MF significantly arrested cells in G2 and M phases, apparently sensitizing the cells to RT. CONCLUSIONS: MF may inhibit A549 cells and can increase their sensitivity to RT, possibly by affecting cell cycle- and apoptosis-related signaling pathways.

[Expression of a protein peak(3144 m/z) in serum and its clinical significance in patients with gastric cancer].

OBJECTIVE: To investigate the expression of protein peak (3144 m/z) in serum and of its association with clinical pathological characteristics and prognosis in patients with gastric cancer. METHODS: Three hundred and twenty seven pathologically confirmed gastric cancer patients were recruited from February 2006 to October 2008 in the Zhejiang Cancer Hospital. SELDI-TOF-MS was employed to detect the expression of protein peak (3144 m/z) in preoperative serum. RESULTS: The positive rate of 3144 m/z protein peak was 33.9% (111/327), significantly higher than that of CEA (21.1%,69/327), and the difference was statistically significant (P<0.01). The positive rate of combined detection of protein peak (3144 m/z)and CEA was 45.6% (149/327). The expression of protein peak (3144 m/z) was associated with clinical staging (P<0.01), nervous invasion (P<0.01), tumor size (P<0.01), vascular invasion (P<0.05), lymph node metastasis (P<0.05), expression of CEA (P<0.05), and depth of infiltration (P<0.05). Significant difference was observed in 3-year survival rate between the patients with protein peak and patients without protein peak (44.7% vs. 64.4%, P<0.01). However, 3144 m/z protein peak was not an independent prognostic factor on multivariate Cox regression analysis (P=0.057). CONCLUSION: Protein peak (3144 m/z) may be used as a diagnostic or prognostic marker of gastric cancer.

[Use of serum protein profiling for early diagnosis of gastric cancer].

OBJECTIVES: To identify serum biomarkers associated with early gastric cancer. METHODS: Serum proteins or peptides were purified with weak cation exchange magnetic beads in 433 patients with gastric cancer and 120 healthy subjects. Distinct peaks were selected using Biomarker Wizard software. The area under receiver operating characteristic curve(AUC) was generated to analyze discrimination capability of peaks between gastric cancers and health people. RESULTS: Thirteen distinct peaks were identified between 42 gastric cancer and 42 health people matched by age and gender(P<0.001). There were 5 peaks (2745, 2768, 6629, 3402, and 6436 m/z) with AUC greater than 0.8. Peak of 6629 m/z was identified to be transthyretin. The sensitivity and specificity of 6629 m/z were 65.5% and 92.0%. The sensitivity of 6629 m/z was 59.4% in I(A gastric cancer. CONCLUSION: Transthyretin precursor may be of value in the early diagnosis of gastric cancer.

Screening of the metastasis-associated genes by gene chip in high metastatic human ovarian cancer cell lines.

Affymetrix U133A oligonucleotide microarrays were used to study the differences of gene expressions between high (H) metastatic ovarian cancer cell line, HO-8910PM, and normal ovarian tissues (C), bioinformatics was used to identify their chromosomal localizations. A total of 1,237 genes were found to have a difference in expression levels more than eight times. Among them 597 were upregulated (Signal Log Ratio[SLR] > or = 3), and 640 genes were downregulated (SLR< or =-3). Except one gene, whose location was unknown, all these genes were randomly distributed on all the chromosomes. However, chromosome 1 contained the most differentially expressed genes (115 genes, 9.3%), followed by chromosome 2 (94 genes, 7.6%), chromosome 12 (88 genes, 7.1%), chromosome 11 (76 genes, 6.1%), chromosomes X (71 genes, 5.7%), and chromosomes 17 (69 genes, 5.6%). These genes were localized on short-arm of chromosome (q), which had 805 (65.1%) genes, and the short arms of No.13, 14, 15, 21, and 22 chromosomes were the only parts of the chromosomes where the differentially expressed genes were localized. Functional classification showed that most of the genes (306 genes, 24.7%) belonged to the enzymes and their regulator groups. The subsequent group was the nucleic acid binding genes (144 genes, 11.6%). The rest of the top two groups were signal transduction genes (137 genes, 11.1%) and proteins binding genes (116 genes, 9.4%). These comprised 56.8% of all the differentially expressed genes. There were also 207 genes whose functions were unknown (16.7 %). Therefore it was concluded that differentially expressed genes in high metastatic ovarian cancer cell were supposed to be randomly distributed across the genome, but the majority were found on chromosomes 1, 2, 12, 11, 17, and X. Abnormality in four groups of genes, including in enzyme and its regulator, nucleic acid binding, signal transduction and protein binding associated genes, might play important roles in ovarian cancer metastasis. Those genes need to be further studied.

[Screening of carcinogenesis associated genes in gastric carcinoma by gene chip].

OBJECTIVE: To screen the carcinogenesis associated genes in gastric carcinoma by gene chip. METHODS: U133A (Affymetrix Santa Clara, CA) gene chip was used to detect differentially expressed genes in tumor tissues, paratumor mucosa and normal mucosa. Bioinformatics was used to analyze the screened results. RESULTS: A total of 150 genes were detected with a difference of expression levels more than 3 times in paratumor mucosa compared with normal gastric mucosa, 130 of which were up-regulated and 20 down-regulated. According to the function classifications of the differentially expressed genes, the most common ones were enzyme and enzyme regulon activity associated genes(28, 18.7% ). The frequencies of nuclei acid binding activity associated genes,signal transduction associated genes and protein binding associated genes were 11.3%, 10%, and 8.7% respectively. Seventy-one differentially expressed genes were detected both in tumor tissues and paratumor mucosa compared with normal mucosa, 61 of which were up-regulated and 10 down-regulated. Among these 71 genes,e leven genes were localized on chromosome 19, 6 on chromosome 1, 2, 16, 17 respectively. No abnormal differentially expressed gene were detected on chromosome 5, 14, 22 and Y. CONCLUSIONS: These 71 genes differentially expressed both in tumor tissues and paratumor mucosa may be associated with carcinogenesis of gastric carcinoma. The four kinds of genes associated with enzyme and enzyme regulon activity, nuclei acid binding activity, signal transduction, and protein binding should be the main genes for the study of carcinogenesis in gastric carcinoma.

[Study on gene expression profile difference in gastric cancer, pericancerous mucosa and normal gastric mucosa from the distant cutting margin by oligonucleotide microarray].

OBJECTIVE: To study the difference of gene expression profiles in gastric cancer (T), pericancerous mucosa (P) and the gastric mucosa from distant cutting margin (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results. RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found,with a difference of more than four times in expression levels, including 530 up-regulated [Signal Log Ratio (SLR) > 2], and 236 down-regulated (SLR< -2). When P was compared with C, 64 genes were found, with a difference of more than four times in expression levels, including 50 up-regulated (SLR > 2), and 14 down-regulated (SLR< -2). Compared with C, a total of 143 genes with a difference of more than four times in expression levels both in T and P tissues. Of the 143 genes, 108 were up-regulated (SLR > 2), and 35 were down-regulated (SLR< -2). CONCLUSIONS: Gene chip can reveal 143 same genes both in pericancerous mucosa and gastric mucosa. These genes may be related to the carcinogenesis and development of early gastric cancer.