The Expression Of NGX6 MRNA And Some Important Proteins In The WNT Signaling Pathway In Colorectal Cancer By Tissue Microarrays

Tissue microarray(TMA)is a biochip,these analytical tool have developed into a powerful tool for the high-throughput analysis of tissue specimens for the past few years. Tissue microarrays contain between tens and hundreds of Tissue material from tumour and normal tissue.According to predesign systematic arrangement,tissue microarrays can combine with RT-PCR,in situ hybridization(ISH)and immunohistochemical(ICH) analysis,confirming the results of microarray experiments at both the transcriptional and the proteomic level.These techniques have been contribution for diagnosis,therapy and prognosis.Colorectal Cancer(CRC)is a common malignant tumor.Metastasis and invasion are the Mainly reason death of CRC patient.Colorectal tumorigenesis is mainly by aberrant activation of the WNT signaling pathway.Beta-catenin is the central signalling molecule of the canonical WNT pathway,where it activates target genes,such as cyclinD1,c-myc and c-jun,in a complex with LEF/TCF transcription factors in the nucleus.Although the significance of these events is not entirely clear,oncoprotein overexpression may be directly involved in the tumorigenic mechanism.NGX6(Nasopharyngeal carcinoma related protein gene),which was isolated by Molecular genetics laboratory of Cancer Research Institute of Central South University with position- candidate cloning strategy.Previous studies showed that NGX6 was down-regulated in colorectal carcinomas and the expression of NGX6 in colorectal carcinomas with lymph-node or distance metastasis(15/16)was significantly lower than that without metastasis.The cancer cells from nasopharynx and colorectum transfected by NGX6 can induce the reversion of some malignant phenotypies and down-regulation of the important molecules in EGFR signaling pathway.These studies reveals that NGX6 may play a negative role in the invasion and metastasis of Colorectal cancer and nasopharyngeal carcinoma.In this study,we examined the expression of the protein level of Beta-catenin,TCF4, cyclin D1,c-myc,c-jun and the mRNA level of the NGX6 gene in 336 Colorectal tissue cores using tissue microarray analysis.Immunohistochemical analysis of Beta-catenin, TCF4,cyclin D1,c-myc,c-jun,but NGX6 mRNA expression was detected in situ hybridization.CONCLUSIONS:1.Relationship between the different location of mucosa in colorectal Tissue Microarray: the expression of the protein level of Beta-catenin,TCF4,cyclin D1,c-myc,c-jun and the mRNA level of the NGX6 gene were significantly disparity in the different location of mucosa in the same colorectal tissue.2.Relationship between the expression and clinicopathological parameters in colorectal Tissue Microarray:The protein expression of beta-catenin and cyclin D1 was correlated with Duke's stages and histological grade,respectively;The expression of NGX6 mRNA was correlated with Duke's stages,tumor size and lymph node metastasis in the Colorectal Cancer.The expression of c-jun was correlated with tumer locum.High protein expression level of TCF4 and c-jun did not show a correlation with gender,age,histological grade, Duke's stages,lymph node metastasis and distant metastasis.3.Correlation between the different target in the same colorectal cancer tissue:There were Correlation between the different target in the same colorectal cancer tissue.4.Primary tumor and lymph node metastasis:The protein expression of TCF4,c-myc and c-jun was significantly difference in both primary tumors and lymph node metastasis tissue;But not with the expression of Beta-catenin,cyclin D1 and NGX6 mRNA.