Expression And Clinical Significance Of CDK11 In Hepatocelluar Carcinoma

Background Hepatocellular carcinoma(HCC)is highly invasive and metastatic,with high morbidity and mortality.It is one of the most common malignant tumors in China.At present,the most important treatment is surgical resection,but because there is no obvious discomfort in its early stage,most patients have been in the late stage of HCC when diagnosed,and lost the best opportunity for operation.Even after surgery,the prognosis of patients with HCC is not satisfactory,because HCC is very easy to relapse and occur distant metastasis.The pathogenesis of HCC and its molecular mechanism are not fully understood yet.It is currently believed that the occurrence of HCC is a complex process with multiple factors and steps.The main cause of HCC in China is hepatitis B virus or hepatitis C virus infection.In developed countries,alcohol is the main cause.In addition,there are some other reasons for HCC,such as sex hormones,aflatoxins,nitrosamines and trace elements.In recent years,with the advancement of radiotherapy and chemotherapy technology and the research of molecularly targeted drugs,the quality of life and survival time of patients with advanced HCC have been impressively improved.However,most patients cannot tolerate the side effects associated with drug treatment,and may also lead to drug resistance then reduce the therapeutic effect of drugs.Therefore,exploring new molecular markers that could predict HCC early is of great significance for improving the detection rate of HCC and the quality of life of patients with HCC.The cell cycle is a indispensible process for cell proliferation in various organisms and is regulated by cyclins and cyclin-dependent kinases.A large number of evidence have reported that cyclin and cyclin-dependent kinase are important in the development of various tumors.CDK11 is a member of the serine/threonine kinase family and plays vital roles in transcription,autophagy and apoptosis,and is highly expressed in a variety of tumors,which plays an important role in the regulation of its development.However,the expression level and functional role of CDK11 in HCC have not been reported yet.In this study,we first used TCGA database and gene enrichment analysis to find that CDK11 was highly expressed in HCC tissues,and was positively correlated with TNM staging,and high expression of CDK11 predicts poor survival rate.Subsequently,the expression level of CDK11 protein in HCC tissues was significantly higher than that in normal tissues by immunohistochemical technique.Cox regression analysis showed that CDK11 was an independent risk factor affecting the prognosis of patients with HCC,and HCC patients with high CDK11 expression had a poor prognosis.Objective The purpose of this study was to analyze the expression of CDK11 in pan-carcinoma,especially in hepatocellular carcinoma(HCC),and its clinical significance with the prognosis of HCC patients by using tissue immunohistochemistry combined with bioinformatics technology and network public tumor data platform(TCGA and HPA,etc).Methods 1.CAAT,an online analysis website based on TCGA database,was used to analyze the expression of CDK11 in pan-cancer tissues and corresponding paracancerous tissues.2.Using TCGA-LIHC dataset to analyze the expression of CDK11 in liver cancer,and analyze its relationship with survival and prognosis of liver cancer patients.3.Tissue microarray immunohistochemical staining was used to verify the relationship between the expression of CDK11 protein and clinicopathological features and prognosis in hepatocellular carcinoma(HCC).4.Statistical analysis of biological data is performed using R language,Graph Pad Prism 6.0 and SPSS 23.0 software.All data are expressed in Mean ± SD.Kaplan-Meier method is used to map the survival curve of CDK11 expression and prognosis of patients then perform log-rank test.Univariate and multivariate analyses are performed using Cox risk regression analysis.Comparison between the two sets of data is applied Students' t-tests.? = 0.05 as the inspection level.Results 1.The expression of CDK11 m RNA was significantly different in many kinds of tumors.2.The expression level of CDK11 m RNA was significantly higher in HCC tissues than in the adjacent tissues,and the difference was statistically significant.The high expression of CDK11 was positively correlated with TNM stage.The KM survival curve analysis showed that HCC patients with high CDK11 levels had a significantly shorter survival time than that of patients with low expression of CDK11.3.The CDK11 protein in HCC tissues was higher than that in adjacent tissues(P=0.0002).The expression of CDK11 in HCC patients with stage TNM stage I-II was lower than that in patients with stage III-IV(P=0.0149).Kaplan-Meier analysis showed that patients with high CDK11 expression had shorter survival time than patients with low CDK11 expression(HR=1.837,P=0.0005).In addition,CDK11 was positively correlated with TNM stage(P = 0.003)and cirrhosis(P = 0.015),but there was no significant correlation with age(P = 0.706),gender(P =0.871),tumor size(P = 0.247))and pathological differentiation(P=0.747).Cox univariate and multivariate analysis showed that CDK11 expression(HR=1.997,P=0.024)and TNM stage(HR=2.514,P=0.003)were both independent risk factors for HCC prognosis.Conclusion 1.The expression of CDK11 was different in multiple tumors,and the expression of CDK11 was increased in HCC.2.The high expression of CDK11 indicated a more malignant clinical features and a worse survival prognosis of patients with HCC,which might become a novel biomarker for early diagnosis of HCC and a potential target for HCC therapy.