| Background:Colorectal cancer(CRC)is one of the most common malignant tumors of the digestive system in the world,and the incidence and mortality of colorectal cancer are still increasing.The occurrence and development of colorectal cancer is a long and complex pathological process involving multiple genes.At present,the molecular mechanism is not very clear,mainly related to the imbalance of tumor suppressor gene and oncogene activity.The most important pathway for the occurrence of colorectal cancer is presently the traditional“ adenoma-carcinoma ”pathway.Most colorectal cancer develops through this pathway,that is,there is a sequential phenomenon of normal colorectal mucosa → adenoma → colorectal cancer in the occurrence and development of colorectal cancer.Colorectal adenoma is a benign tumor composed of mucosal glandular epithelium of colorectal dysplasia,and is also one of the recognized precancerous lesions of colorectal cancer.It is of great significance to detect adenoma in time and perform endoscopic resection for reducing the incidence and mortality of colorectal cancer.Among them,tubular adenoma is often accompanied by mild and moderate dysplasia with low malignant conversion rate,and villous adenoma is often accompanied by severe dysplasia with high malignant conversion rate.Timely detection and resection of adenoma is of great significance to reduce the incidence and mortality of colorectal carcinoma.Endoplasmic reticulum protein 29(ERp29)has been confirmed to be down-regulated or absent in many malignant tumors,including colorectal cancer.At present,most studies have shown that the expression level of ERp29 is negatively correlated with tumor progression and positively correlated with prognosis,but the exact regulatory effect and molecular mechanism of ERp29 remain to be further studied.Wnt signaling pathway is involved in the occurrence of various human tumors,and plays an important role in regulating the occurrence,development,invasion and metastasis of colorectal cancer.Among them,β-catenin in the classical Wnt signaling pathway is the key factor involved in the regulation of the signaling pathway.For tumors dominated by Wnt signaling pathway,when the β-catenin was stimulated by Wnt signaling,it gradually accumulated in the cytoplasm and transferred to the nucleus,positively regulating the expression of downstream related target genes,leading to excessive proliferation and abnormal differentiation of normal cells.Studies have shown that β-catenin is highly expressed in the nucleus of breast cancer.After ERp29 transfection,the high expression of ERp29 in this cell will make β-catenin shift to the cytoplasm,thereby blocking the transcriptional activity of Wnt pathway.Some studies have shown that ERp29 can reduce the expression of downstream transcription products after activation of Wnt signaling pathway,suggesting that ERp29 plays a negative role in regulating the signaling pathway.However,in the malignant transformation process of colorectal adenoma-adenocarcinoma,the relationship between ERp29 and Wnt pathway has not been systematically studied by retrieving relevant literature.Objective:In this study,the expression of ERp29 and β-catenin in colorectal tissues at different stages of colorectal canceration and their relationship with clinicopathological features of colorectal adenomas and adenocarcinomas were compared and analyzed by immunohistochemical staining.The exact role of ERp29 and β-catenin in the occurrence and development of colorectal tumors was verified,and the internal relationship and possible mechanism of ERp29 and Wnt/β-catenin pathway in the carcinogenesis of colorectal adenomas were preliminarily explored,providing a basis for exploring the mechanism of disease occurrence and development and potential new prevention and treatment methods of colorectal carcinoma patients.Methods:60 cases of colorectal adenomatous polyp tissue,20 cases of non-adenomatous polyp tissue,40 cases of colorectal adenocarcinoma and 40 cases of corresponding paracancerous tissue were collected.The clinical pathological parameters of colorectal adenoma,non-adenoma and adenocarcinoma were recorded by referring to the medical records.1.En Vision immunohistochemical staining was used to detect the expression of ERp29 and β-catenin in colorectal adenoma,non-adenomatous polyp tissue,colorectal adenocarcinoma and paracancerous tissue,and the expression differences between different tissues were analyzed.2.To analyze the relationship between the expression levels of ERp29 and β-catenin and the clinicopathological parameters of colorectal adenoma and adenocarcinoma.3.To analyze whether the expressions of ERp29 and β-catenin were correlated in colorectal adenoma and adenocarcinoma.4.To analyze the correlation between abnormal expression of ERp29 and β-catenin and malignant tendency of colorectal adenoma and malignant behavior of adenocarcinoma.Results:1.The positive expression rate of ERp29 in adenocarcinoma tissues→adenoma tissues→non-adenomatous polyp tissues was gradually increased,and the positive rate of ERp29 in colorectal adenocarcinoma tissues was significantly lower than that in paracancerous tissues,as well as the adenoma and non-adenomatous polyp tissues(all P<0.01).There was no significant difference in the positive expression rate of ERp29 between adenoma and non-adenomatous polyps(P>0.05).The abnormal expression rate of β-catenin gradually decreased in the order of adenocarcinoma tissues→adenoma tissues→non-adenomatous polyp tissues.The abnormal expression rate of β-catenin in colorectal adenocarcinomas was significantly higher than that in paracancerous tissues,adenoma and non-adenomatous polyp tissues(all P<0.01).The abnormal expression rate of β-catenin in adenoma and non-adenomatous polyp tissues was also significantly different(P<0.01).2.The expression intensity of ERp29 in colorectal adenocarcinomas was significantly lower than that in paracancerous tissues,colorectal adenomas and non-adenomatous polyps(all P<0.01).The expression intensity of ERp29 in colorectal adenoma tissues was lower than that in non-adenomatous polyp tissues,The difference was statistically significant(P<0.05).3.The positive expression rate of ERp29 was not significantly correlated with the histological type and degree of dysplasia of colorectal adenoma(all P>0.05),was significantly negatively correlated with TNM stage and lymph node metastasis(all P<0.01).The abnormal expression of β-catenin in tubular adenoma was significantly lower than that in villous adenoma(P<0.01).The expression of β-catenin in adenoma with mild and moderate dysplasia was significantly lower than that in severe dysplasia(P<0.05).The expression of β-catenin in colorectal carcinoma was positively correlated with differentiation,TNM stage and lymph node metastasis(all P<0.01).The positive expression rates of ERp29 and β-catenin were not significantly correlated with age,gender,diameter,location,and number of adenoma in patients with colorectal adenoma,as well as with age,gender,tumor size,location,depth of invasion(T stage),and tumor thrombus in patients with adenocarcinoma(all P>0.05).4.There was no significant correlation between the positive expression rates of ERp29 protein and β-catenin protein in colorectal adenoma group(P>0.05),but there was a moderate negative correlation between the positive expression rates of ERp29 protein and β-catenin protein in colorectal adenocarcinoma group(P<0.01).5.There was no significant difference in the simultaneous abnormal expression of ERp29 and β-catenin between different histological types and different degrees of dysplasia colorectal adenomas(all P>0.05).However,in colorectal adenocarcinoma tissues,compared with the abnormal expression of single protein,the lower the differentiation degree of colorectal adenocarcinoma,the worse the clinical TNM staging,and the greater the risk of lymph node metastasis,the differences were statistically significant(P<0.05,0.01,0.01).Conclusion:1.ERp29 and β-catenin were involved in the carcinogenesis of colorectal tissues.ERp29 was negatively correlated with the progression of colorectal tumors,andβ-catenin was positively correlated with the progression of colorectal tumors.2.Down-regulation of ERp29 and ectopic expression of β-catenin may be important molecular events in the process of colorectal adenoma carcinogenesis,and throughout all stages of adenoma carcinogenesis.3.Abnormal expression of ERp29 and β-catenin may be associated with malignant transformation of colorectal adenoma and malignant behavior of colorectal cancer.4.There is a certain correlation between the expression level of ERp29 and β-catenin.ERp29 may play an important role in the carcinogenesis of colorectal adenoma due to its down-regulation of expression by some mechanism and lose the negative regulation of Wnt/β-Catenin pathway.5.The combined detection of the expression levels of ERp29 and β-catenin certain significance for more accurate assessment of the malignant degree and metastasis potential of colorectal cancer. |
PDF Full Text Request