Study on The Expression and Correlation of Alpha-Enolase (Eno1) in The Serum of Patients With Hepatocellular Carcinoma

Abstract Background: Serum tumor markers for the early detection of hepatocellular carcinoma is limited. This study analyzed the distribution and differences of ENO1 in the serum of healthy people, patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma. Furthermore, the distribution and correlation of ENO1 in the clinical data of patients with hepatocellular carcinoma were explored and its clinical diagnostic effect as well as combined diagnostic effect with AFP were compared. In addition, the effect of ENO1 on the survival of patients with hepatocellular carcinoma were also evaluated. The study will provide data basis for the application of ENO1 in the diagnosis of hepatocellular carcinoma, and provide new ideas for the study of molecular markers and therapeutic targets for hepatocellular carcinoma.Methods: In accordance with the inclusion and exclusion criteria, Patients diagnosed at the Infectious Diseases Department of the General Hospital of Ningxia Medical University and the healthy check-up population at the medical check-up centre from May 2012 to March 2017 were screened for inclusion in the study. T The final study subjects were 181, 28 patients with chronic hepatitis B (CHB), 31 patients with liver cirrhosis (LC), 104 patients with liver cancer (HCC) and 18 healthy people (NC). Clinical data and sera were collected from all study subjects, tissue specimens were collected from some patients. The levels of serum ENO1 and AFP were measured by ELISA. QRT-PCR and Western Blot t were used to detect the relative expression of ENO1 mRNA and protein in liver cancer tissues and paracancerous tissues. Statistical analysis was performed by t-test, bivariate Spearman correlation test, curve regression analysis, ROC curve analysis and survival curve analysis.Results: The relative expression of ENO1 mRNA and protein was significantly upregulated in hepatocellular carcinoma tissues relative to paraneoplastic tissues (p<0.05), ENO1 levels in the serum of HCC patients were sequentially higher than those of CHB patients, LC patients and healthy subjects, with significant differences (p<0.05). The differences in the distribution of serum ENO1 levels in the clinical data subgroups alpha fetoprotein (AFP) status, TNM stage (II vs III, III vs IV) were not statistically significant (p>0.05), there were statistically significant differences (p<0.05) in the distribution of gender, tumor size, whether the tumor was metastatic or not, TNM stage (I vs II) and Edmondson's grading in the clinical information subgroup. The difference in the distribution among clinical information subgroups of whether the tumor had recurred was highly significant (p < 0.01). Serum ENO1 levels showed a significant positive correlation with AFP levels (Spearman's correlation coefficient 0.312, p=0.001**), the diagnostic sensitivity and specificity of ENO1 in this group of HCC patients were 0.673 and 0.831 (AUC=0.782, cutoff=75.96, p=0.0001), respectively, the sensitivity of ENO1 in conjunction with AFP in the diagnosis of HCC in this group was 0.740 and the specificity was 0.723 (AUC=0.835, p=0.0001), the AUCs of ENO1 in the diagnosis of HCC tumor size, whether the tumor was metastatic, TNM I stage, Edmondson classification and whether the tumor recurred in this group were 0.663 (0.546-0.781, P=0.012*), 0.681 (0.574-0.787, P=0.002**), 0.553 (0.421-0.686, P=0.386), 0.710 (0.602-0.819, P=0.001**), and 0.685 (0.580-0.789, P=0.001**).Conclusion: Serum ENO1 levels were significantly correlated with the occurrence, progression and metastasis of hepatocellular carcinoma, staging and postoperative survival of patients. ENO1 may be a candidate diagnostic marker for early diagnosis and evaluation of hepatocellular carcinoma progression, and can be used in combination with AFP as an auxiliary diagnostic function.