Aberrant methylation of SPARC in human hepatocellular carcinoma and its clinical implication

AIM:To investigate the methylation status of secreted protein acidic and rich in cysteine(SPARC) in human hepatocellular carcinoma(HCC) and evaluate its clinical implication.METHODS:The methylation status of SPARC was analyzed in one HCC cell line(SMMC-7721) and 60 pairs of HCC and corresponding nontumorous tissues by methylation-specific polymerase chain reaction and bisulfite sequencing.The expression of SPARC mRNA and protein were examined by reverse transcription polymerase chain reaction and immunohistochemistry,respectively.The correlations between the methylation status and the gene expression,the clinicopathological parameters,as well as the prognosis after surgery were analyzed.RESULTS:In the SMMC-7721 cell line,the loss of SPARC expression was correlated with the aberrant methylation and could be reactivated by the demethylating agent 5-aza-2'-deoxycytidine.Methylation frequency of SPARC in HCC was significantly higher than that in the corresponding nontumorous tissues(45/60 vs 7/60,P < 0.001),and it was correlated with the pathological classification(P = 0.019).The downregulation of the SPARC mRNA expression in HCC was correlated with the SPARC methylation(P = 0.040).The patients with methylated SPARC had a poorer overall survival than those without methylated SPARC(28.0 mo vs 41.0 mo,P = 0.043).CONCLUSION:Aberrant methylation is an important mechanism for SPARC inactivation in HCC and SPARC methylation may be a promising biomarker for the diagnosis and prognosis of HCC.

Challenges of incorporating gene expression data to predict HCC prognosis in the age of systems biology

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide.The recurrence of HCC after curative treatments is currently a major hurdle.Identification of subsets of patients with distinct prognosis provides an opportunity to tailor therapeutic approaches as well as to select the patients with specific sub-phenotypes for targeted therapy.Thus,the development of gene expression profiles to improve the prediction of HCC prognosis is important for HCC management.Although several gene signatures have been evaluated for the prediction of HCC prognosis,there is no consensus on the predictive power of these signatures.Using systematic approaches to evaluate these signatures and combine them with clinicopathologic information may provide more accurate prediction of HCC prognosis.Recently,Villanueva et al developed a composite prognostic model incorporating gene expression patterns in both tumor and adjacent tissues to predict HCC recurrence.In this commentary,we summarize the current progress in using gene signatures to predict HCC prognosis,and discuss the importance,existing issues and future research directions in this field.

Survival Analysis of Hepatocellular Carcinoma： A Comparison Between Young Patients and Aged Patients

Background： To compare the clinicopathological features and prognosis between younger and aged patients with hepatocellular carcinoma （HCC）. Methods： We analyzed the outcome of 451 HCC patients underwent liver resection, transcatheter arterial chemoembolization and radiofrequency ablation, respectively. Then risk factors for aged and younger patients＇ survival were evaluated by multivariate analysis, respectively. Results： The patients who were older lhan 55 years old were defined as the older group. The overall survival for aged patients was significantly worse than those younger patients. The younger patients had similar liver fhnctional reserve but more aggressive tumor Paclors than aged patients. Cox regression analysis showed that tile elevated levels ofaspartate aminotransferase （AST） （Waldx2= 3.963, P = 0.047, hazard ratio [HR] -1.453, 95% confidence interval [CI]： 1.006-2.098）, lower albumin （Wald X2 = 12.213, P 〈 0.001, HR 1.982, q5% CI： 1.351 2.910）, tumor size （Wald X2 = 8.179, P- 0,004, HR - 1.841,95% CI： 1.212-2.797）, and higher alpha-fetoprotein level （Wald X2=4.044, P = 0.044, HR = 1,465, 95% （CI： 1.010 2.126） were independent prognostic factors for aged patients, while only elevated levelsofAST（WaldZ= 14.491,P〈0.001,HR 2.285, 95%CI： 1.493-3.496）andtumorsize（WaldX2= 21.662, P〈0.001,HR= 2.928, 95% CI： 1.863-4.604） were independent prognostic factors for younger patients. Conclusions： Age is a risk factor to determine the prognosis of patients with HCC. Aged patients who have good liver lhnctional reserve are still encouraged to receive curative therapy.