| Colorectal cancer(CRC)is one of common tumour in digestive diseases.According to the data from WHO in 2008,there were 1.2 million new cases of CRC all over the world,with about 608700 deaths.In European countries,each year nearly 0.2 million people died from CRC,ranked as the second mortality rate among all malignant tumours.In recent years,the morbidity and mortality of CRC in China are arising.Due to the lack of specific clinical manifestations in the early stage,treatment usually begins until the emergence of abdominal pain,hematochezia,weight loss and other symptoms.Almost 80%of the patients had been diagnosed with metastasis and missed the best time for treatment.Therefore,exploring early molecular markers of CRC has become a research hotspot,and these studies will contribute to early clinical diagnosis and prognostic evaluation of CRC.Klotho is a newly found protein with an anti-aging role,which was closely associated with a variety of chronic and age-related diseases.It was found in early researches that Klotho played a role in anti-aging and regulating metabolism of calcium phosphate.Moreover,recent studies suggested that Klotho was closely related to the development of a variety of tumours.For CRC,our previous studies indicated that Klotho expressed significantly lower or silent expression in cancerous tissue.There were few reports on the dynamic change of Klotho in the progression of CRC.The relationship between its expression level and the clinicopathological features of patients with CRC was also rarely studied.This study aims to detect the dynamic expression of Klotho in different lesions from normal,colorectal adenoma and CRC tissues,both from mice and human,exploring the role of Klotho playing in the process of CRC.Methods1.73 cases of CRC tissues and paracancerous tissues,110 cases of colorectal adenoma tissues and 20 cases of normal colonic tissues were enrolled in our study.The expression of Klotho protein was detected by immunohistochemistry,and the clinical pathological data of age,gender,tumor location,differentiation,TNM stage and lymphatic metastasis were recorded.The survival and prognosis of 73 patients with CRC were followed,and the relationship between the changes of Klotho protein in the process of CRC and its clinical pathological parameters was analyzed.2.Azoxymethane(AOM)and dextran sodium sulfate(DSS)were applied orderly to copy colitis associated colon cancer mouse model.12 male five-week-old C57BL/6 mice were randomly devided into two groups:the control group and model group.The model group mice were injected intraperitoneally with a single dose of 10mg/kg AOM.One week later,the mice were given 3%DSS in their drinking water for 5 days.This was followed by normal water for 16 days.21 days comprised a DSS cycle,and the model mice were treated for 3 DSS cycles.The control group mice were injected intraperitoneally with a same volum of saline,fed with normal drinking water until the end of modeling.All the mice were fed with normal diet.On week 10,all the mice were sacrificed,and colon samples were then collected for histopathological examinations and immunohistochemistry.Results1.276 cases were enrolled in the present study(mean age,60.5 years),including 73 CRC specimes and 73 paracancerous tissues,110 specimes of colorectal adenoma tissues and 20 specimes of normal colorectal tissues.There were 41 males and 28 females in the CRC group(mean age,62.97±11.42 years).For the colorectal adenoma group,it was constituted of 72 males and 38 females(mean age,56.47±9.27 years),and 14 males and 16 females were in the healthy control group(mean age,49.9±13.02 years).There was no statistical difference in the general data among these three groups.2.By IHC,it was found that during the progression from normal lesion→adenoma→cancer,the expression of Klotho protein in colorectal tissue was gradually decreasing.Furthermore,Klotho expression in CRC tissues was significantly correlated with tumour differentiation,lymph node metastasis,distant metastasis and TNM stage(P<0.05).3.By applying AOM and DSS,we successfully built up the colitits-associated colorectal cancer model.The results of immunohistochemical staining found that the expression level of Klotho gradually decreased in the process of normal lesion→adenoma or atypical hyperplasia→cancer.ConclusionThe protein expression level of Klotho gradually decreased in the process of CRC.Down regulation of Klotho expression is an early marker of the occurrence of colorectal cancer. |
PDF Full Text Request