结直肠癌趋化因子IP—10的表达

目的：通过检测结直肠癌组织中干扰素诱生蛋白－10（IP－10）的表达情况，研究IP－10的表达与结直肠癌浸润、转移等生物学行为的关系。方法：采用RT－PCR方法检测临床收集的新鲜结直肠癌组织标本中IP－10mRNA的表达；采用免疫组织化学方法检测结直肠癌组织中IP－10蛋白的表达。结果：12例结直肠癌组织经RT－PCR检测9例出现IP－10mRNA的表达，40例结直肠癌组织IP－10蛋白表达的阳性率为87．5％；结直肠癌组织IP－10蛋白的表达与结直肠癌的转移及Dukes分期呈负相关，IP－10表达强者，肿瘤转移发生率低，Dukes分期早。结论：结直肠癌组织中IP－10的表达能影响结直肠癌的浸润、转移等生物学行为。

Overexpression of S100A4 is closely associated with progression of colorectal cancer

AIM： To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS： A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS： Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 （55.6%） of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 （69.4%） of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes＇ stage and lymph node metastasis. Nuclear staining was also observed in 24 （19.4%） of 124 samples and closely associated with Dukes＇ stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION： Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.

Polo-like kinase 1 expression is a prognostic factor in human colon cancer

AIM：To clarify the expression patterns and prognostic implications of the mitotic regulator Polo-like kinase 1 （PLK1） in colon cancer. METHODS： Expression of PLK1 was investigated by immunohistochemistry （158 cases） and immunoblotting in tissue of colon adenomas and adenocarcinomas. PLK1 expression patterns were correlated with clinicopathological parameters and patient prognosis. In addition, expression of PLK1 was evaluated by immunoblot and PCR in colon carcinoma cell lines, and coexpression of PLK1 with the proliferation marker Ki-67 was investigated. RESULTS： Weak PLK1 expression was observed in normal colon mucosa and adenomas. In contrast, 66.7% of carcinomas showed strong expression of PLK1. Overexpression of PLK1 correlated positively with Dukes stage （P〈0.001）, tumor stage （P = 0.001） and nodal status （P〈0.05）. Additionally, PLK1 expression was a prognostic marker in univariate survival analysis （P〈0.01） and had independent prognostic significance （RR = 3.3, P = 0.02） in patients with Iocoregional disease. Expression of PLK1 mRNA and protein was detected in all cell lines investigated. Coexpression of PLK1 and Ki-67 was observed in the majority of colon cancer cells, but a considerable proportion of cells showed PLK1 positivity without Ki-67 expression. CONCLUSION： PLK1 is a new prognostic marker for colon carcinoma patients and may be involved in tumorigenesis and progression of colon cancer. Strategies focusing on PLK1 inhibitionin vivo might therefore represent a promising new therapeutic approach for this tumor entity. 2005 The WIG Press and Elsevier Inc. All rights reserved

Tiaml gene expression and its significance in colorectal carcinoma

AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiaml gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptase-polymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiaml expression with the invasive ability was also analyzed. RESULTS: Tiaml gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116, LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiaml gene was highly related to the metastatic potential of colorectal carcinoma cells. CONCLUSION: Tiaml gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

Telomerase activity and human telomerase reverse transcriptase expression in colorectal carcinoma

AIM： To study the activity of telomerase and the expression of human telomerase reverse transcriptase （hTERT） in colorectal carcinoma and its adjacent tissues, normal mucosa and adenomatoid polyp, and to evaluate their relation with carcinogenesis and progression of colorectal carcinoma. METHODS： Telomerase activity and hTERT expression were determined in 30 samples of colorectal carcinoma and its adjacent tissues, normal mucosa and 20 samples of adenomatoid polyp by modified telomeric repeat amplification protocol （TRAP）, enzyme-linked immunosorbent assay （ELISA） and immunohistochemical method. RESULTS： Telomerase activity and hTERT expression were 83.33% （25/30） and 76.67% （23/30） respectively in colorectal carcinoma, which were obviously higher than those in paracancerous tissues （13.33%, 16.67%）, normal mucosa （3.33%, 3.33%） and adenomatoid polyp （10%, 10%）. There was a significant difference between colorectal carcinoma and other tissues （P=0.027）. The telomerase activity and hTERT expression were higher in colorectal carcinoma with lymphatic metastasis than in that without lymphatic metastasis （P=0.034）. When the histological classification and clinical stage were greater, the telomerase activity and hTERT expression increased, but there was no significant difference between them. In colorectal carcinoma, the telomerase activity was correlated with hTERT expression （positive vs negative expression of telomerase activity and hTERT, P=0.021）. CONCLUSION： Telomerase activity is closely correlated with the occurrence, development and metastasis of colorectal carcinoma. Overexpression of hTERT may play a critical role in the regulation of telomerase activity.

Lysophosphatidic acid transactivates both c-Met and epidermal growth factor receptor, and induces cyclooxygenase-2 expression in human colon cancer LoVo cells

AIM： To examine whether lysophosphatidic acid （LPA） induces phosphorylation of c-Met and epidermal growth factor receptor （EGFR）, both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 （COX-2） expression in human colon cancer cells. METHODS： Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis, followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis. RESULTS： Immunoprecipitation analysis revealed that 10 μmol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 IJmol/L LPA induced COX-2 expression in a dose-dependent manner. CONCLUSION： Our results suggest that LPA acts upstream of various receptor tyrosine kinases （RTKs） and COX-2, and thus may act as a potent stimulator of colorectal cancer. 2005 The WJG Press and Elsevier Inc. All rights reserved.

Reduced expression ofβ-catenin inhibitor Chibby in colon carcinoma cell lines

AIM： To analyse the Chibby expression and its function in colon carcinoma cell lines and colorectal carcinoma （CRC）. METHODS： Chibby expression levels were investigated by quantitative RT-PCR in a panel of seven different colon carcinoma cell lines. By sequencing, we analysed mutational status of Chibby. To test whether Chibby exhibited effects on β-catenin signalling in colon carcinoma cells, we transfected SW480 cells with Chibby expression plasmid and, subsequently, analysed activity of β-catenin and tested for alterations in cellular phenotype. In addition, we examined Chibby mRNA levels in samples of colorectal carcinomas and adjacent normal tissues by using quantitative RT-PCR and hybridised gene chips with samples from CRC and normal tissues. RESULTS： Chibby mRNA expression was strongly downregulated in colon carcinoma cell lines in comparison to normal colon epithelial cells and no mutation in any of the examined colon carcinoma cell lines was found. Further, we could show that Chibby inhibited β-catenin activity in TOPflash assays when over-expressed in SW480 cells. Proliferation and invasion assays with Chibby transfected SW480 cells did not reveal profound differences compared to control cells. In contrast to these in vitro data, quantitative RT-PCR analyses of Chibby mRNA levels in CRC tumor samples did not show significant differences to specimens in adjacent non-cancerous tissue. Consistent with these findings, gene chips analysing tissue samples of tumors and corresponding normal tissue did not show altered Chibby expressionCONCLUSION： Altered Chibby expression might be observed in vitro in different colon carcinoma cell lines. However, this finding could not be confirmed in vitro in CRC tumors, indicating that Chibby is not likely to promote CRC tumor development or progression. As Chibby is an important inhibitor of β-catenin signalling, our data implicate that the usability of colon carcinoma cell lines for in vitro studies analysing the Wnt/β-catenin pathway in colorectal carcinoma needs extensive verification.

DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor

AIM： TO determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis. METHODS： The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis. RESULTS： A statistical found in both adenomas y significant difference was and carcinomas as compared to matched normal colonic mucosa （P〈0.00）. However, changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86 nuclear expression, as determined by Western blot and immunohistochemical analyses （P〈0.001）. Cytoplasmic protein expression was found in pathological samples, but not in normal tissues either from tumor patients or from healthy subjects. CONCLUSION： Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.

Expression of ST13 in colorectal cancer and adjacent normal tissues

AIM: To investigate the in situ expression of suppressionof tumorigenecity 13 (ST13) mRNA in both colorectal cancer and adjacent normal tissues.METHODS: Colorectal cancer cell lines SW1116, SW620and CoLo205 were enrolled to confirm the feasibility of the in situ hybridization procedure. Seven colorectal cancer and adjacent normal tissues were included for RNA-RNA in situ hybridization.RESULTS: The expression of ST13 in the seven normal colon tissues was positive and the positive signals appeared in mucosal cells. Only three of the seven colorectal cancer tissues had positive hybridization signals that appeared in adenocarcinoma cells.CONCLUSION: The expression of ST13 decreases in colorectal cancer tissue compared with that in adjacent normal tissue. ST13 is mostly expressed in colorectal epithelia and adenocarcinoma cells.

Pin1 overexpression in colorectal cancer and its correlation with aberrant β-catenin expression

AIM： To investigate clinical significance of Pin1 and β-catenin expression in colorectal cancers and to demonstrate the relationship of their expression. METHODS： The role of Pin1 and β-catenin protein in colorectal tumorigenesis and their clinicopathologic significance were analyzed by immunohistochemistry, and correlation between Pin1 and β-catenin protein expressions was also studied in 124 patients with colorectal cancer who were surgically treated. RESULTS： Normal colonic epithelium either failed to express or showed focal and weak expression of Pin1 and β-catenin. Overexpression of Pin1 and β-catenin protein was found in 23 （18.54%） and 50 （40.3%） of 124 colorectal cancers, respectively. Overexpression of both proteins was not related to the lymph node metastasis, tumor stage and survival period after excision. Survival analysis results indicated that tumor stage was a valuable predictor of survival. Interestingly, a significant correlation was found between Pin1 and β-catenin protein expression. CONCLUSION： Overexpression of Pin1 and β-catenin may be closely related with the development and/or progression of colorectal carcinoma and further supports that Pin1 overexpression might contribute to the upregulation of β-catenin.

B_7 molecule mRNA expression in colorectal carcinoma

AIM： To observe the status of tumor-associated B7 molecule mRNA expression in human colorectal cancer tissue by/n situ hybridization. METHODS： The mRNA expression patterns of cancer- associated B7-1,B7H1t,B7H2, ICOS in 22 specimens of human colorectal cancer tissue were monitored by in situ hybridization （ISH） with digoxin-labeled oligonucleotide probes. RESULTS： B7-1, B7H1,B7H2,ICOS mRNA were detected in both cancer cells and tumor infiltrating lymphocytes （TIL）. The mRNA expression level of these molecules in tumor cells was higher than that in TIL （0.76±0.54-1.62±0.82 vs 0.38±0.19-0.65±0.33, P〈0.001）. There was no relationship between expression level of tested B7 family molecules and patients＇ sex, age, differentiation status of cancer and regional lymph node metastasis. CONCLUSION： Th2 cytokine predominant in tumor microenvironment might be related to the expression of B7H1t B7H2 co-signal molecules in tumor cells and TIL. 2005 The WJG Press and Elsevier Inc. All rights reserved

Gene expression profiling:Canonical molecular changes and clinicopathological features in sporadic colorectal cancers

AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction （RT-PCR）. RESULTS： The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair （NMR） defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis （P 〈 0.001）. Amongst 47 differentially expressed genes, seven （PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS） were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory. CONCLUSION： We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.

Aberrant expression of krUppel-like factor 6 protein in colorectal cancers

AIM： TO investigate whether krüppel-like factor 6 （KLF6） plays an important role in the development and/or progression of colorectal cancer. METHODS： A total of 123 formalin-fixed and paraffinembedded colorectal cancer specimens were analyzed by immunohistochemistry using tissue microarray for the expression of KLF6 protein. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. The correlation of KLF6 expression with clinicopathologic parameters was analyzed by χ^2 test and Bartholomew test. RESULTS： Normal colonic epithelium showed weak to moderate expression of KLF6, whereas reduced KLF 6 expression or loss of KLF6 expression was seen in 45 （36.6%） of the 123 colorectal carcinoma specimens. Interestingly, aberrant expression of KLF6 was detected in 25 （43.1%） of 58 cases with metastasis to regional lymph node and in 31 （47.0%） of 66 tumors more than 5 cm in size. Statistically, loss of KLF6 expression was significantly associated with tumor size （P〈0.05）. However, there was no significant correlation between KLF6 expression and Dukes＇ stage （Bartholomew test, P〉 0.05）, tumor location and lymph node metastasis （χ^2 test, P〉0.05）.CONCLUSION： Loss of KLF6 expression may be a common and early event in colorectal carcinogenesis.

Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers

AIM:To investigate the polymorphic simple sequencerepeat in intron 1 of the epidermal growth factor receptorgene(EGFR)(CA-SSRⅠ),which is known to affect theefficiency of gene transcription as a putative target of themismatch repair(MMR)machinery in colorectal tumors.METHODS:The CA-SSRⅠgenotype was analyzed ina total of 86 primary colorectal tumors,selected upontheir microsatellite instability(MSI)status[42 with highfrequency MSI(MSI-H)and 44 microsatellite stable(MSS)]and their respective normal tissue.The effect of the CA-SSRⅠgenotype on the expression of the EGFR gene wasevaluated in 18 specimens using quantitative real-timereverse transcription PCR and immunohistochemistry.RESULTS:Mutations in CA-SSRⅠwere detected in 86%(36 of 42)of MSI-H colorectal tumors and 0%(0 of 44)ofMSS tumors,indicating the EGFR gene as a novel putativespecific target of the defective MMR system(P<0.001).Impaired expression of EGFR was detected in most ofthe colorectal tumors analyzed[6/12(50%)at the mRNAlevel and 15/18(83%)at the peptide level].However,noassociation was apparent between EGFR expression andCA-SSRⅠstatus in tumors or normal tissues.CONCLUSION:Our results suggest that CA-SSRⅠsequence does not contribute to the regulation of EGFRtranscription in colon,and should thus not be consideredas a promising predictive marker for response to EGFRinhibitors in patients with colorectal cancer.

Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity

AIM： To evaluate the role of N-myc downstream- regulated gene 1 （NDRG1） expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds. METHODS： Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α （HIF-1α）, we examined NDRG1 expression together with p53 and HIF-1α by irnmunohistochernistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed. RESULTS： NDRG1 protein was significantly increased in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion, venous invasion, depth of invasion, histopathological type, and Dukes＇ stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type, Dukes＇ stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly, Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However, in p53-positive US cases, NDRG1 positivity correlated significantly with better survival. In addition, NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and IV tumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors, strong NDRG1 staining in p53- positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy. CONCLUSION： NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.

Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma

AIM： To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS： Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNE） were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma. RESULTS： The survivin positive unit （PU） was higher in cancerous tissues （38.76±5.14） than in para-cancerous （25.17±7.26） or normal tissues （0.57±0.03） （P〈0.05）. The apoptosis index （AI） of para-cancerous tissues was （7.51±2.63%） higher than cancerous tissues （4.65±1.76%）. The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma. CONCLUSION： Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.

The expression of chemokine MCP-1 in colorectal carcinoma and its relationship to the infiltration of macrophage

Objective: To study the expression of MCP-1 in colorectal carcinoma and its relationship to the infiltration of the macrophage and to the biological behaviour of infiltration and metastasis of colorectal carcinoma. Methods: The expression of the MCP-1 mRNA was assessed in colorectal carcinoma collected freshly from surgical specimen by RT-PCR and the expres- sion of the MCP-1 protein was assessed in colorectal carcinoma collected from surgical specimen by immunohistochemistry. The tumor infiltrating cell and macrophage were also investigated by immunohistochemistry. Results: All the 12 specimens of colorectal carcinoma detected by RT-PCR expressed the MCP-1 mRNA; MCP-1 protein was detected in 90℅ (36/40) cases of the tumor; The expression of the MCP-1 protein in colorectal carcinoma correlated negatively with its state of metastasis and the Dukes’ stage. But a postive correlation was found between the expression of MCP-1 and the infiltrated macrophage. The stron- ger expression of MCP-1, the more number of the infiltrated macrophage. Conclusion: The expression of chemokine MCP-1 in colorectal carcinoma may influence its biological behaviour of infiltration and metastasis, and can attract the immuno-cell to the local of the tumor, such as Macrophage.

Identification of differently expressed genes in human colorectal adenocarcinoma

AIM： To investigate the differently expressed genes in human colorectal adenocarcinorna.METHODS： The integrated approach for gene expression profiling that couples suppression subtractive hybridization, high-throughput cDNA array, sequencing, bioinformatics analysis, and reverse transcriptase real- time quantitative polymerase chain reaction （PCR） was carried out. A set of cDNA clones including 1260 SSH inserts amplified by PCR was arrayed using robotic printing. The cDNA arrays were hybridized with florescent-labeled probes prepared from RNA of human colorectal adenocarcinoma （HCRAC） and normal colorectal tissues.RESULTS： A total of 86 genes were identified, 16 unknown genes and 70 known genes. The transcription factor Sox9 influencing cell differentiation was downregulated. At the same time, Heat shock protein 10 KDis downregulated and Calmoulin is up-regulated.CONCLUSION： Downregulation of heat shock protein 10 KD lost its inhibition of Ras, and men attenuated the Ras GTPase signaling pathway, increased cell proliferation and inhibited cell apoptosis. Down-regulated transcription factor Sox9 influences cell differentiation and cell-specific gene expression. Down-regulated Sox9 also decreases its binding to calmodulin, accumulates calmodulin as receptor-activated kinase and phosphorylase kinase due to the activation of PhK.

Effect of NS398 on metastasis-associated gene expression in a human colon cancer cell line

AIM： To investigate the effect of NS398 on the metastasis-associated gene expression in LoVo colorectal cancer cells.METHODS： LoVo cells were treated with NS398 at the concentration of 100 IJmol/L for 24 and 48 h respectively. Total RNA was extracted with TRIzol reagents and reverse transcribed with Superscript Ⅱ and hybridized with cDNA mlcroarray （containing oncogenes, tumor suppressor genes, signal transduction molecules, adhesive molecules, growth factors, and ESTs） fabricated in our laboratory. After normalization, the ratio of gene expression of NS398 treated to untreated LoVo cells was either 2-fold up or 0.5-fold down was defined as the differentially expressed genes. Semi-quantitative RT-PCR was used to validate the microarray results.RESULTS： Among the 447 metastasis-associated genes, 9 genes were upregulated and 8 genes were downregulated in LoVo cells treated with NS398 for 24 h compared to untreated cells. While 31 genes were upregulated and 14 genes were downregulated in LoVo cells treated with NS398 for 48 h. IGFBP-5, PAI-2, JUN,REL, BRCA1, and BRCA2 might be the new targets of NS398 in treatment of colorectal cancer.CONCLUSION： NS398 might exert its anti-metastasis effect on colorectal cancer by affecting several metastasis-associated gene expression.

Evaluation of ST13 gene expression in colorectal cancer patients

We identified a novel gene ST13 from a subtraetive eDNA library of normal intestinal mueosa in 1993, more studies showed that ST13 was a co-chaperone of Hsp70s. Recently we detected the ST13 gene expression in tumor tissue and adjacent normal tissue of the same colorectal cancer patient and investigated if the ST13 gene expression might have any prognostic value. Analysis was performed at molecular level by reverse transcription-PCR using real-time detection method. We measured two genes simultaneously, ST13 as the target gene and glyceraldehydes-3-phosphate dehydrogenase as a reference gene, in primary colorectal tumor specimens and tumor-adjacent normal mucosa specimens from 50 colorectal cancer patients. The expression levels of the ST13 gene were significantly decreased in primary tumors compared with adjacent mucosa （P〈0.05）. But there were no significant differences in the expression of ST13 as compared depth, lymph node metastasis and disease-specific survival. with different Dukes＇ stage, tumor differentiation grade, invasion