| BackgroundPrimary liver cancer is the fourth most common malignant tumor in China and the third leading cause of cancer death[1,2],which is the sixth leading cause of the incidence of malignant tumor in the world[3],and has become one of the main causes of economic burden in developing countries[4].The primary liver cancers mainly include Hepatocellular Carcinoma?HCC?,Intrahepatic Cholangiocarcinoma?ICC?and HCC-ICC mixed types[5].Among them,HCC accounts for more than 85-90%of all liver tumors,so the liver cancer in the text mainly refers to HCC Hepatitis virus,chronic alcoholism,non-alcoholic steatohepatitis,and aflatoxin-contaminated foods are high risk factors for HCC.HBV and HCV infections are relatively clear pathogenic factors leading to the occurrence of HCC.With the development of science and technology,the treatment of HCC has also made great progress.Surgical resection,liver transplantation,and radiofrequency ablation provide an opportunity for prolonging the survival time of liver cancer patients[6].However,the majority of patients with liver cancer have been diagnosed with advanced stage of HCC and lost the opportunity for surgical treatment.Furthermore,the intrahepatic and extrahepatic metastasis of liver cancer is also a major cause of poor prognosis and high recurrence rate[7].However,no effective detection markers have been found to predict the occurrence of HCC and to guide the treatment of liver cancer.Alpha-fetoprotein?AFP?,a specific serum marker of liver cancer,is the most widely used tumor marker of liver cancer at present.It is mostly used for postoperative monitoring and therapeutic evaluation,but its sensitivity is low,and 30%of patients with liver cancer have AFP negative[5].Therefore,it is particularly important to look for new molecular markers of liver cancer,improve early diagnosis rate and find new targets for liver cancer treatment.With the continuous deepening of research on the level of cancer gene molecules,more and more genes,proteins,and signaling pathways related to malignant phenotypes of HCC,such as staging,recurrence,and metastasis have been discovered,and they play an extremely important role in the process of the formation and progression of HCC.The metastasis and recurrence of cancer cells is a complicated process.Both intrinsic factors and external microenvironment may affect the occurrence of metastasis of liver cancer cells[8].Therefore,through in-depth research on the molecular mechanisms involved in liver cancer,exploring effective targeting molecules for HCC recurrence and metastasis can greatly improve the overall prognosis of patients with liver cancer.Although important studies on liver cancer mainly focus on oncogenes and tumor suppressor genes,the importance of tumor cell metabolism has recently been emphasized[9].The metabolism of tumor cell is called the Warburg effect[10,11],and the glucose metabolism of cancer cell is mainly transformed into glycolysis through the process called“aerobic glycolysis”.Studies have demonstrated that increased glucose intake and aerobic glycolysis are features of tumor metabolism,and key enzyme analysis of these pathways provides a direction for targeted therapy.Alpha-enolase?ENO1?is a key enzyme in the pentose phosphate pathway[12].It is highly expressed in various tumors[13-15],such as gastric cancer,renal cell carcinoma,and glioma and so on,and plays an important role in the occurrence and development of tumor.Similarly,studies have shown that ENO1 is also highly expressed in HCC and play an oncogene role[16].However,due to the limited number of samples used in the study,it is necessary to further confirm the results of the study.In this study,we combined bioinformatics knowledge and used the CAAT?Canna Atlas Analysis Tools?,an on-line analysis database set up by the research group,to analyze pan-neoplastic tissue samples and mRNA expression profiles of liver cancers in TCGA and GEO,and to perform joint analysis using tissue chip technology.The expression differences of ENO1 in HCC were verified from mRNA and protein levels,and the relationship between ENO1 expression and clinical prognosis of patients with liver cancer was analyzed.ObjectiveBased on bioinformatics technology and public network data platform,we intend to analyze the expression of ENO1 in pan-tumor and HCC and its relationship with the survival and prognosis of patients with HCC,and analyzes its clinical significance.Methods1.Analysis of ENO1 expression in pan-tumor gene chip using CAAT?Cancer Atlas Analysis Tools?online analysis database;2.Using TCGA,GEO gene expression profile data to analyze the expression of ENO1mRNA in HCC,and the relationship between the expression of ENO1 and clinicopathological features and prognosis was analyzed;3.Immunohistochemical staining of tissue microarray was used to verify the expression level of ENO1 protein in HCC and its relationship with prognosis;4.Statistical analysis was performed using Graph Pad Prism 5.0 and SPSS 21.0 software.The method of comparison between the two sets of data is a two-sided Student's t-test or Mann-Whitney's test.All data were expressed as mean±standard deviation.The Kaplan-Meier survival curve was used to analyze the relationship between gene expression and prognosis.?=0.05 was used as the test level.Results1.Abnormal expression of ENO1 in pan-tumor tissues and high expression in HCC;2.The expression level of ENO1 mRNA was significantly higher in HCC tissues than in adjacent tissues,and the difference was statistically significant.Univariate analysis suggested that the expression of ENO1 was different in patients with different TNM staging?P=0.023?and pathological grade?P=0.008?.However,there was no significant correlation between the expression level of ENO1 and race?P=0.698?,age?P=2.258?,gender?P=0.453?,histological type?P=0.514?.The results of COX multivariate analysis suggested that the expression level of ENO1?HR 1.916,P=0.002?and TNM staging?HR 2.462,P=0.000?were independent risk factors for the prognosis of HCC;3.The expression level of ENO1 protein in TNM stage?-?was lower than that in stage?-?of HCC,and the difference was statistically significant?Z=?2.042 P=0.041?.Kaplan-Meier analysis suggested that the survival time of HCC patients with high expression of ENO1 was shorter than patients with low expression of ENO1?HR=1.837,P=0.0435?.Conclusion1.Abnormal expression of ENO1 in pan-ntumor tissues and high expression in HCC.2.The high expression of ENO1 is associated with the malignant clinical phenotype and shorter overall survival of patients with liver cancer,and has potential value for early diagnosis and targeted therapy of HCC. |
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