| Objective: Colorectal tubular adenoma is the most common pathological type of colorectal adenoma. Carcinogenic transformation of colorectal tubular adenoma is not uncommonly seen in clinical practice. But the research of the mechanism is seldom. Abrrant crypt foci (ACF) is thought to be the earliest and smallest identifiable neoplastic lesions be observed under light microscope during the colorectal carcinogenesis. Dysplastic ACFs may progress to adenoma. Normal mucosa - aberrant crypt foci - adenoma - carcinoma sequence has been confirmed from genetics, biology and signal transduction pathway etc.NGX6 is a new tumor inhibitory factor, variety of methods have proved NGX6 gene expression decreased or even missing in colon cancer, especially in distant metastasis colorectal cancer, it significantly lower expressed can also be found in nasopharyngeal cancer, lung cancer, liver cancer et al. It is suggested that NGX6 may have the functions of inhibit tumor proliferation and metastasis. Studies have found that NGX6 have a regulation relationship with ILK and c-Jun, which are very important in the Wnt and JNK / SAPK signal transduction pathway. NGX6 over expression can lead to Wnt /β-catenin signaling pathway related molecules ILK expression decreased. It can also down regulate EGFR/K-ras/JNK/c-Jun/cyclin D1 signaling pathway related molecules such as JNK and c-Jun, to play a role of tumer inhibition.Integrin-linked kinase (ILK) is an intracellular signaling protein involved in a variety of Wnt signal transduction, it plays an important role in the regulation of cell adhesion, apoptosis, metastasis, tumor formation. The study found that, ILK high expressed in gastric carcinoma, cervical carcinoma, non-small cell lung cancer, prostate cancer, melanoma, ovarian carcinoma, et al, and the level of expression has a positive correlation with the malignant degree of tumor cells and the ability of infiltration and metastasis, it is suggested the abnormal expression of ILK may lead to tumor formation.C-Jun is an important downstream target genes regulated by JNK. C-Jun is the first gene be identified related to the intracellular signaling. It is considered to be a rapidly early response genes, it is also a proto-oncogene that regulats the cell proliferation and differentiation, the high expresstion can be found in carcinoma of breast, ovarian carcinoma, esophageal squamous cell carcinoma and other malignant tumors.To further explore the mechanism carcinogenesis of sporadic colorectal tubular adenoma. The expression of NGX6, ILK and c-Jun in normal colorectal mucosa, dysplastic ACF, sporadic colorectal tubular adenoma with different dysplasia and colorectal tubular adenoma with cancerous changes were comparatively studied with pathological observation, immunohistochemical staining, and analysis the relevance of the three. The aim of our study was to provide a theoretical basis to early diagnosis and treatment of the colorectal tubular adenoma.Method: The expression of NGX6, ILK and c-Jun was studied in 22 cases dysplastic ACFs, 68 cases of sporadic colorectal tubular adenoma with different dysplasia, 21 cases of colorectal tubulare adenoma with cancerous changes and 21 cases of normal colorectal mucosa with S-P immunohistochemical method. The experimental data were analyzed with Chi-square test, Fisher exact probability calculation method and correlation with stastics software of SPSS13.0 edition.Results:1 The expression of NGX6 in the carcinogenesis of colorectal adenomaThe positive expression rate of NGX6 was 85.71%, 77.27%, 50.00%, and 28.57% respectively in normal colorectal mucosa, dysplastic ACFs, sporadic colorectal tubular adenoma with different dysplasia and colorectal tubular adenoma with cancerous changes. The positive expression of NGX6 was higher in the cases of ACF than that of colorectal tubular adenoma with different dysplasia , the difference was statistically significant (P <0.05). The positive expression of NGX6 was higher in the cases of normal colorectal mucosa than that of colorectal tubular adenoma with sever dysplasia, the difference was statistically significant (P <0.05). In the cases of colorectal tubular adenoma with mild, moderate and sever dysplasia, the NGX6 protein positive expression rates were 70.83%, 37.50% and 35.00%. The positive expression rate of NGX6 in colorectal tubular adenoma with mild dysplasia is significantly higher than the degree of moderate and sever dysplasia, the difference was statistically significant(P<0.05); The positive expression rate in ACF is significantly higher than tubular adenoma with moderate and sever dysplasia, the difference was statistically significant(P<0.05).2 The expression of ILK in the carcinogenesis of colorectal adenomaThe positive expression rate of ILK was 0%, 9.09%, 35.29%, 76.19%, respectively in normal colorectal mucosa, dysplastic ACFs, sporadic colorectal tubular adenoma with different dysplasia and colorectal tubular adenoma with cancerous changes. The positive expression rate of ILK is lower in the cases of ACF than that of colorectal tubular adenoma with different dysplasia , the difference was statistically significant (P <0.05); the positive expression rate of ILK is lower in the cases of colorectal tubular adenoma with different dysplasia than that of colorectal tubular adenoma with cancerous changes, the difference was statistically significant (P <0.05). In the cases of colorectal tubular adenoma with mild, moderate and sever dysplasia, the ILK protein positive expression rates was 20.83%, 29.17% and 60.00%, the positive expression of colorectal tubular adenoma with sever dysplasia is significantly lower than the degree of mild and moderate dysplasia, the difference is statistically significant (P<0.05). The positive expression rate of ILK was lower in the cases of ACF, colorectal tubular adenoma with mild and moderate dysplasia than that of colorectal tubular adenoma with sever dysplasia, the difference was statistically significant (P <0.05).3 The expression of c-Jun in the carcinogenesis of colorectal adenomaThe positive expression rate of c-Jun was 9.52%, 45.45%, 77.94%, 85.71%, respectively in normal colorectal mucosa, dysplastic ACFs, sporadic colorectal tubular adenoma with different dysplasia and colorectal tubular adenoma with cancerous changes. The positive expression rate of c-Jun is higher in the cases of ACF than that of the cases of normal colorectal mucosa, the difference was statistically significant (P <0.05); the positive expression rate of c-Jun is higher in the cases of colorectal tubular adenoma with different dysplasia than that of ACF, the difference was statistically significant (P <0.05). In the cases of colorectal tubular adenoma with mild, moderate and sever dysplasia, the ILK protein positive expression rates was 70.83%, 75.00% and 90.00%, The positive expression rate of c-Jun is lower in the cases of ACF than that of the cases of colorectal tubular adenoma with moderate and sever dysplasia, the difference was statistically significant (P <0.05).4 Relationship among NGX6, ILK and c-Jun expression in the carcinogenesis of sporadic colorectal adenomaIn the dysplastic ACFs, sporadic colorectal tubular adenoma with dyslasia and colorectal tubular adenoma with cancerous changes, negative correlation could be found among the expression of NGX6 with ILK and c-Jun (P<0.05). Positive correlation could be found between the expression of ILK and c-Jun(P<0.05). Negative relationship between the expression NGX6 and ILK(P<0.05), NGX6 and c-Jun(P<0.05), positive relationship between ILK and c-Jun(P<0.05) could be found in dysplastic ACFs and colorectal tubular adenoma with different dyslasia.5 Relation between the expression of NGX6, ILK, c-Jun and the clinical pahtological significanceThe results showed, the expression of NGX6 and c-Jun were not related with location, sex, and age (P>0.05).The expression of ILK was not related to location and sex (P>0.05), but it is related to the age of patients, the positive expression rate of cases that younger than 40 years old is 80%(8/10), the cases of older than 40 years old is 40.59%(41/101). There was obviously difference between the cases that older and younger than 40 years old(P<0.05). Conclusion:1 The positive expression rate of NGX6 was decreased in the sporadic colorectal tubular adenoma with different dysplasia and colorectal tubular adenoma with cancerous changes. Indicating that NGX6 expression may play a role in the colorectal adenoma formation and carcinogenesis.2 The positive expression rate of ILK and C-Jun was increased in the sporadic colorectal tubular adenoma with different dysplasia and colorectal tubular adenoma with cancerous changes. Indicating that ILK and C-Jun expression may play a role in the colorectal adenoma formation and carcinogenesis.3 C-Jun was high expressed in dysplastic ACFs, suggested that c-Jun may play a role in the processe of forming ACF.4 Thus the results suggest that, negative correlation could be found among the expression of NGX6 with ILK and c-Jun. Positive correlation could be found between the expression of ILK and c-Jun; thus the results suggest that NGX6 regulate the expression of ILK and c-Jun negatively. Thereby contributing to the formation of dysplasia ACF and adenoma, promoting the carcinogenesis of sporadic colorectal tubular adenoma incidence. |
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