Expression Of RECQL4 In Hepatocellular Carcinoma And Its Association With Clinical Pathologic Characteristics Of Patients

Objective: The tumorigenesis of hepatocellular carcinoma(HCC)is a complex process and is influenced by multiple genes and multiple factors.In our previous cDNA microarray experiments,we discovered that RECQL4 gene was overexpressed in HCC tissues.RECQL4,as one of human DNA helicases,plays a critical role in maintaining the stability of the genome.Genomic instability is an important cause of carcinogenesis.However,the exact role of RECQL4 in the development of HCC remains unknown.This study aims to investigate RECQL4 expression in HCC and further analyze its potential clinical implication in HCC patients.Methods: The expression of RECQL4 mRNA was detected in 205 cases of HCC tissues and corresponding adjacent normal liver tissues(ANLT)by quantitative real-time polymerase chain reaction(qRT-PCR)in our study.And the relationship between the expression level of RECQL4 gene and the clinicopathological features of HCC patients was analyzed by chi-square test.The influences of RECQL4 on disease-free survival(DFS)and overall survival(OS)were tested by the Kaplan–Meier method,univariate analysis and multivariate analysis using Cox proportional hazard regression model.Results: The results qRT-PCR showed that the expression of RECQL4 mRNA in HCC tissues(1.10 ± 0.07)was significantly higher than that in adjacent normal liver tissues(ANLT)(0.33 ± 0.04)(P < 0.001).The RECQL4 mRNA expression level was positively associated with serum a-fetoprotein(AFP)level(> 100 ng/ml)(χ2 = 4.246,P = 0.039),tumor size(> 6 cm)(χ2 = 7.852,P = 0.005),and Barcelona Clinic Liver Cancer(BCLC)stage(χ2 = 6.293,P = 0.012).Of the 205 HCC patients,AFP alone elevated in 34 cases(16.59%),RECQL4 alone increased in 45 cases(21.95%),and both of them increased in 96 cases(46.83%).Kaplan-Meier survival analysis indicated that HCC patients with a higher RECQL4 mRNA expression had a significantly shorter DFS(34.23 months;95% confidence interval [CI],28.42-40.03)and OS(38.37 months;95% CI,32.84-43.90),when compared with the DFS(50.73 months,95% CI,41.88-59.58)and OS(56.31 months,95% CI,48.33-64.30)in those with low RECQL4 mRNA expression(P = 0.002 and P = 0.001,respectively).Moreover,the 1-,2-,3-,and 5-year OS rates were significantly lower in the HCC patients with high RECQL4 mRNA expression(67.07%、 48.15%、39.05%、32.82%)than in the patients with low RECQL4 mRNA expression(89.50%,70.08%,63.32%,57.88%).Besides high RECQL4 mRNA,size of tumor > 6 cm,multiple tumor number,B-C of BCLC stage,and metastasis,were also strongly associated with a shorter OFS and OS,and postoperative tumor recurrence was associated with a shorter OS(all P < 0.05).Multivariate survival analysis showed that high RECQL4 expression was a significantly independent predictor of DFS(hazard ratio [HR],1.635;95% CI,1.062-2.515;p = 0.025)and OS(HR,1.618;95% CI,1.050-2.493;p = 0.029)for HCC patients.Conclusions: The expression of RECQL4 gene was significantly elevated in HCC tissue,and it might serve as an effective novel biomarker for early diagnosis and prognosis in HCC patients.