Expression Of Hes1and Hes2is Associated With Prognosis After Curative Resection Of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and the5thleading cause of cancer-related deaths worldwide. Although radical hepatectomy isconsidered as one of the first line treatment for patients with early HCC, the surgicaloutcome is far from satisfactory due to the likelihood of intrahepatic and extrahepaticrecurrence. Meanwhile, the number of the early stage HCC patients who undergo hepaticresection has been gradually increasing as a result of progresses in the surveillance andearly detection. Although great efforts have been made for investigating precise prognosticbiomarker for early HCC, the optimal candidates with clinical applicability are still lackingand urgently required. Therefore, it is clinically meaningful that metastasis and prognosisrelated molecule and its functional mechanism were found. In this study, we detected Hes1and Hes2expression in paired HCC tissues and adjacent tissues at first, and then combinedwith clinical acse analysis, the relationship between expression of Hes1or Hes2and theprognosis of HCC patients undergoing curative resection was evaluated based on that Hes1or Hes2was overexpressed in HCC tissues, and as a theoretical and clinical basis fortherapeutic targets of HCC.Part Ⅰ The expression of Hes1and Hes2in tissue of hepatocellularcarcinomaAims: To detect Hes1and Hes2expression in paired HCC tissues and adjacent tissues.Methods: Detect the expression of Hes1and Hes2through RT-PCR、western blot andImmunohistochemistry, and then prospective observational the consecutive enrolled330patients who underwent radical resection of hepatocellular carcinoma from January2007to December2008. Results: All RT-PCR、western blot and Immunohistochemistry indicated that Hes1andHes2expression in tumor tissues is lower than that the paired adjacent tissues.Part Ⅱ The relationship between the expression of Hes1and Hes2andthe prognosis of hepatocellular carcinomaAims: To detect the relationship between Hes1or Hes2expression and the prognosis ofHCC patients who undergoing curative resection.Methods:1. Case informationWe study a total of400cases of radical resection of liver cancer patients in Shanghai EastHepatobiliary Surgery Hospital from January2007to December2008. After screening theexclusion criteria,330cases of liver cancer are included in our study.2. Surgical approachThe criteria of radical resection is that all tumors are completely removed; no residualtumor confirmed by intraoperative B ultrasound; negative cutting edge by histologicalexamination; the high preoperative AFP level declines to normal in2months; nointrahepatic new lesions2months after the operation by imaging examination.3. Follow-upAll patients underwent standardized follow-up. The end of follow-up time was December2010, with a median follow-up time18months.4. Statistical methodsTime to recurrence (TTR) and overall survival were considered the primary endpoints.TTR was calculated from the date of resection to the date when tumor recurrence wasdiagnosed; overall survival was calculated from the date of resection to the date of death orlast follow-up. All statistical analyses were performed with SPSS version18.0software.The χ~2test or Fisher’s exact test were used to compare qualitative variables, whilecontinuous variables were compared using Student t test or Mann-Whitney test forvariables with an abnormal distribution. Receiver operating characteristic curve analysiswas used to determine the optimal cutoffs of continuous variables. Survival curves werecalculated using the Kaplan-Meier method and compared using a log-rank test. The Coxproportional hazards model was used to determine the independent factors on survival andrecurrence, based on the variables selected on univariate analysis. P <0.05was considered statistically significant.Results: Hes1and Hes2expression in tumor tissues is lower than that the paired adjacenttissues and patients who with high Hes1and Hes2expression had better prognosis thanthose with low expression. Then further study indicated that the expression level of Hes1was also an independent prognostic factor for BCLC0/A stage patients.Conclusion: The patients who with low Hes1and Hes2expression had a worse prognosisthan those with high expression.