The Expression And Clinicopathologic Significance Of CUTL1in Hepatocellular Carcinoma

ObjectiveHepatocellular carcinoma(HCC) is one of the most common malignant carcinomas in China and even in the whole world. It ranks the third in the mortality of all malignant carcinomas in the world. And its incidence rate is still elevating. As the great progression in precaution, prognosis and therapy,we are more capable to treat HCC. Based on the investigation,from year1992to year2004,the survival rate in2-4years has elevated as twice the number as before.However,the survival rate in one year is still below50%.As the research of disease has went into molecular level,people find that the development of many diseases is related to changes of molecular. Transcriptional factor CUTL1,also named CDP、 Cut、Cux and so on,is a CCAAT transplacemental protein,which belongs to a homedomain transcriptional factor family and is conservative in evolution. As studied before, CUTL1plays an important role in modifying cell differentiation、 promoting cell proliferation and promoting progression of cell cycle and so on. And many studies has proved that CUTL1promotes the occurrence and development of colon cancer, breast cancer, uterine fibroids, pancreatic cancer and other malignanciesBased on this,Ⅰ have studied the relationship between CUTL1(cut like1, or CCAAT displacement protein) and HCC In this experiment,first I investigated the difference of expression of CUTL1mRNA and protein between HCC tissue and para-neoplastic tissue. Then I studied the relationship between the level of CUTL1protein and HCC clinicopathologic factors in HCC.At last, I studied the effect of CUTL1protein to the prognosis of HCC patients by Cox proportional hazards model and Kaplan-Meirer survival analysis. All of these reveal that CUTL1may play a role in tumorigenesis,invasion and migration of HCC,thus provides us a new angle towards HCC. Methods1、36cases of HCC and corresponding para-neoplastic tissue were collected from patients who have undertaken HCC resection in Xiangya hospital between February2013to July2013.In order to find the difference of CUTL1mRNA and protein expression between HCC tissue and para-neoplastic tissue, all the samples were detected by real-time fluorescent quantitative PCR and Western-blot to analyze the expression of CUTL1mRNA and protein.Then the relationship of the level between CUTL1mRNA and protein was analyzed by Spearman correlation analysis.2、136cases of HCC specimens from partial HCC patients who have undertaken HCC resection from January2007to January2008were collected. All specimens were studied by immunohistochemistry to confirm the expression level of CUTL1protein. Then I analyzed the relationship between the expression of CUTL1protein and clinicopathologic factors. At last I studied the effect of CUTL1protein to the prognosis of HCC patients.Result1. As shown from real-time-PCR and Western-blot, CUTL1mRNA and protein were expressed in both para-neoplastic tissue and HCC,but the expression level in HCC was obviously higher than the other two tissues (P<0.05). And from Pearson correlation analysis, the expression of CUTL1mRNA and protein was positively related.2. Immunohistochemistry revealed that the expression of CUTL1protein was mainly in nucleus of hepatocyte, which was consistent with its role as a transcription factor. Based on the clinicopathologic analysis, I found that the expression of CUTL1protein was positively correlate with Edmondson grading(P<0.05) of HCC. And in vascular invasion group and large tumor size group there was higher expression of CUTL1protein than the others in HCC(P<0.05). In contrast, CUTL1protein expression level had no obvious correlation with the patient age, gender, cirrhosis or not, tumor number and AFP(P>0.05). 3.Survival analysis showed that the survival phase was obviously shorter in patients with high CUTLlprotein expression than low CUTL1protein expression(P<0.05). Positive CUTL1expression is an important risk factor in prognosis of HCC patients.Conclusion1. The expression of CUTL1protein is mainly in nucleus of hepatocyte, which means it functions mainly in nucleus, which is consistent with the role of transcription.2. Based on the result of Western-blot and real-time-PCR, the expression of CUTL1protein and mRNA in HCC was obviously higher than para-neoplastic tissue, so we can come to a conclusion that CUTL1may play a important role in the development of HCC.3. Based on the analysis of the relationship between CUTL1protein and clinicopathologic factors, which the expression of CUTL1protein is positively correlate with Edmondson grading, vascular invasion and tumor diameter of HCC, we can come to the conclusion that CUTL1may play an important role which promotes development, invasion, immigration of HCC. Survival analysis showed that expression CUTL1may not be conducive to the prognosis of patients with hepatocellular carcinoma.