Identification of exon mutations of the CDX1 gene in children with congenital anorectal malformation / 中华消化外科杂志

Objective To explore the distribution of exon mutations of CDX1 gene in children with congenital anorectal malformation (ARM).Methods In a case-control study conducted between June 2003 and March 2009,108 children with congenital ARM and 120 normal children undergoing health examinations who were admitted to the Shengjing Hospital of China Medical University (85 children with congenital ARM and 60 normal children) and the Affiliated Hospital of Hebei University (23 children with congenital ARM and 60 normal children) were assigned to the case group and the control group,respectively.PCR was performed to extend exons of the CDX1 gene and then sequence analysis was conducted after genomic DNAs were extracted from the peripheral blood.Categorical data with normal distribution were presented as (x) ± s and analyzed using the t test,count data were analyzed using the chi-square test.Results Exon sequencing was performed in the case group.Four children with 4 mutations of CDX1 located at coding regions were detected,including 1 with archostegnosis,1 with rectoperineal fistula,1 with rectovestibular fistula and 1 with rectourethral fistula.Four mutations located at the highly conserved homology domain of the CDX1 gene.The mutations of 1 child located at exon 1 of CDX1 gene (c.213-214Ins GAA).The mutations of 2 children located at the splicing region to exon 3 of the CDX1 gene (c.6G ＞ C,c.27G ＞ T).The mutations of 1 child located at the idiocratic splicing region to exon 3 of the CDX1 gene(c.18A ＞ C).No mutation was detected in the controls.Mutations of the CDX1 gene at c.213-214Ins GAA,c.6G ＞ C,c.27G ＞ T,and c.18A ＞ C,respectively,resulted in amino acid substitutions at 96-98Ins E,K199N,R206S,and Q203H in the protein.Conclusion Exon 1 or 3 mutations of the CDX1 gene is identified in children with congenital ARM,and CDX1 gene may be a susceptibility gene for ARM.

CDX1 and CDX2 Expression in Intestinal Metaplasia, Dysplasia and Gastric Cancer

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.

Expressions of caudal type homeodomain transcription factors CDX1 and CDX2 in intestinal metaplasia and gastric carcinoma / 中国医师进修杂志

Objective To study the expressions of caudal type homeodomain transcription factors CDX1 and CDX2 in different subtype of intestinal metaplasia (IM) and gastric eareinoma,and investigate their roles in the development and progression of IM and gastric carcinogenesis, and determine the relationship between IM and gastric carcinoma. Methods Forty eases of chronic superficial gastritis, 40 cases of chronic atrophic gastritis (CAG), 46 eases of CAG with IM, 40 cases of gastric carcinoma, and 32 eases of IM foci in para-eancerous tissues were selected respectively to construct tissue microarrays. Immunohistechemistry and in situ hybridization were used to assess the expressions of CDX2 protein and CDX1, CDX2 mRNA in different gastric lesions respectively. Results The proportion of type Ⅲ IM in IM foci in para-caucerous tissues was significantly higher than that in CAG (56.25% vs 21.74% ,P< 0.01). There was no expression of CDX1, CDX2 mRNA and CDX2 protein in chronic superficial gastritis and CAG without IM. The expression of CDX2 protein and CDX2 mRNA in CAG with IM, para-cancerous tissues and gastric carcinoma was 69.57%, 53.12%,42.50% (CDX2 protein) and 63.04%,46.88%,35.00% (CDX2 mRNA), respectively. The exprossions of CDX1 mRNA in above throe gastric lesions were 67.39%, 50.00%, 40.00%, respectively. The expressions of CDX2 protein and CDX2, CDX1 mRNA in gastric carcinoma were significantly lower than those in CAG with IM (P< 0.01). But there was no significant difference between gastric carcinoma and IM foci in para-cancerous tissues (P> 0.05). Furthermoro,the expressions of CDX2 protein were significantly associated with histological type of gastric carcinoma, which in intestinal-type was significantly higher than those in diffuse-type(54.55% vs 27.78%, P< 0.05). The expression of CDX2 protein in type Ⅲ IM was also significantly lower than that in type Ⅰ IM(46.43% vs 79.31%,P< 0.05). Conclusions CDX1 and CDX2 may play important roles in the development and progression of IM and gastric carcinoma, and may be new gastric carcinoma associated genes. Type Ⅲ IM is a precancerous lesion of the intestinal-type gastric carcinoma.

Homeobox genes CDX1 and CDX2 reduced malignancy of esophageal adenocarcinoma cells / 基础医学与临床

Objective To study the effect of homeobox genes CDX1 and CDX2 on the phenotype of esophageal adenocarcinoma cells.Methods Esophageal adenocarcinoma cell line SEG-1 was transfected with CDX1 or CDX2 cDNA.The morphology,growth rate,division index and tumorigenicity were analyzed.Results The expression of CDX1 or CDX2 leaded to occurring adeniform-like manifestation.The growth rate,division index and tumorigenicity were reduced,especially by CDX2.Conclusion CDX1 and CDX2 all could increase differentiation of esophageal adenocarcinoma cells and reduction of its malignancy.

Relationships Between the Expressions of CDX1 and CDX2 mRNA and Clinicopathologic Features in Colorectal Cancers

BACKGROUND: CDX1 and CDX2 are members of the caudal-type homeobox gene family and control the proliferation and differentiation of intestinal mucosal cells. Their expressions are commonly reduced in colorectal cancer, but reports about the relationships between their expressions and clinicopathologic features are rare. The aim of this study was to examine the expressions of CDX1 and CDX2 mRNAs in colorectal cancers and to assess the relationships between their expressions and clinicopathologic features. METHODS: CDX1 and CDX2 mRNA expressions were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and in adjacent non-tumorous normal mucosal tissue. RESULTS: CDX1 and CDX2 mRNA expressions were significantly reduced in colorectal cancer tissues versus normal mucosal tissues (p=0.001, p=0.042, respectively). As compared with paired normal mucosal tissues, colorectal tissues showed reduced CDX1 mRNA expression in 64.6% (31/48) and reduced CDX2 mRNA expression in 66.7% (32/48) of cases. A statistically significant positive correlation was found between the expressions of CDX1 mRNA and CDX2 mRNA in colorectal cancer (r=0.543, p< 0.001). However, the expressions of CDX1 and CDX2 mRNAs were not related to age, sex, cancer location, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage or serum carcinoembryonic antigen level. CONCLUSIONS: CDX1 and CDX2 mRNA expressions were found to be significantly reduced in colorectal cancers, but these expressional changes were not found to be related to clinicopathologic features.

Relationship of CDX1 mRNA and CDX2 mRNA expression and clinicopathologic features in colorectal cancers / 대한내과학회지

BACKGROUND: CDX1 and CDX2, members of the caudal-type homeobox gene family, control proliferation and differentiation of intestinal mucosal cells. Their expression is reduced commonly in colorectal cancers, but reports about the relationship between their expression and the clinicopathologic features are rare. The aim of this study was to examine CDX1 mRNA and CDX2 mRNA expression in colorectal cancers and to assess the relationship between their expression and the clinicopathologic features. METHODS: CDX1 mRNA and CDX2 mRNA expression were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and their adjacent non-tumorous normal mucosas. RESULTS: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers than in normal mucosas (p=0.001, p=0.042, respectively). In comparison with paired normal mucosas, colorectal cancers showed decreased CDX1 mRNA expression in 64.6% (31/48) and decreased CDX2 mRNA expression in 66.7% (32/48). There was a statistically significant correlation between CDX1 mRNA and CDX2 mRNA expression in colorectal cancers (r=0.543, p<0.001). CDX1 mRNA and CDX2 mRNA expression were not related to age, sex, location of cancer, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage and serum carcinoembryonic antigen level in colorectal cancers. CONCLUSION: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers, but were not related to the clininopathologic features.