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Research Of Early Clinical Outcome And Long-term Prognostic Molecular Factor In Hepatocellular Carcinoma

Posted on:2016-09-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:F Q LiuFull Text:PDF
GTID:1224330461476657Subject:Oncology
Abstract/Summary:PDF Full Text Request
[Objective] To analyze the association of microRNA related single nucleotide polymorphism (SNP) with long-term prognosis of hepatocellular carcinoma (HCC).[Methods] Firstly,26 microRNA-related-SNPs associated with oncogenesis and development of HCC were screened out by using bioinformatics methods. Then, the genotypes of the above 26 SNPs were detected through Sequenom SNP genotyping assay. Many factors to be considered, including serum levels of alpha-fetoprotein (AFP), TNM staging (AJCC,2010), Karnofsky performance score (KPS), hepatic cirrhosis and surgery, the associations between 26 SNPs with overall survival (OS) in 614 patients with HCC were analyzed by Stastic Analysis System 8.2 (Version 8.2, Cary, NC:SAS Institute Inc, USA).[Results] Serum levels of alpha-fetoprotein (AFP), TNM staging (AJCC,2010), Karnofsky performance score (KPS), hepatic cirrhosis and surgery have respectively significant associations with OS. Three miRNA-related-SNPs (rs 11078662, rs 12450517 and rs78312845) were found to have significant correlation with OS. Patients with rs11078662 AG+AA genotype had a significantly longer OS compared than those carrying the GG (HR=0.782,95%CI 0.643-0.950, P=0.0132), as well as rs12450517 AG+AA genotype have improved OS compared with the GG (HR=0.785,95 %CI 0.646-0.955, P=0.0154) and rs78312845 GA+GG genotype have improved OS compared with the AA (HR=0.777,95%CI 0.639-0.946, P=0.0121). The other 23 SNPs have no significant associations with OS.[Conclusions] With multi-factors of serum levels of alpha-fetoprotein (AFP), TNM staging (AJCC,2010), Karnofsky performance score (KPS), hepatic cirrhosis and surgery, three miRNA-related-SNPs (rs11078662, rsl2450517 and rs78312845) were associated with prognosis of HCC patients.[Objective] The influence of early enteral nutrition (EEN) after surgery is still controversial. The early clinical outcomes and cost-effectiveness of postoperative EEN combined with parenteral nutrition (EEN+PN) in patients with hepatocellular carcinoma (HCC) after hepatectomy were assessed according to four years’ clinical experience from a single center. Then to analyze the association of microRNA related single nucleotide polymorphism (SNP) with long-term prognosis of hepatocellular carcinoma (HCC).[Methods] A retrospective comparative design of prospectively collected data from January 2010 through December 2013 was undertaken to compare EEN+PN with total parenteral nutrition (TPN) by dividing 379 HCC patients with the score≥3 of Nutritional Risk Screening 2002 (NRS 2002) into two cohorts (142 patients in EEN+PN study group and 237 patients in TPN control group). The early clinical outcomes of different groups were assessed and contrasted. A decision model was developed to compare the economic outcomes between EEN+PN and TPN. We also divided all patients of two groups into two subgroups respectively (centrally located HCC and non-centrally located HCC, cl-HCC and ncl-HCC) by tumor location and investigate their similarities and differences. The uncertainty and robustness of the results of the model were tested by sensitivity analysis.In basic research,26 microRNA-related-SNPs associated with oncogenesis and development of HCC were screened out by using bioinformatics methods. The genotypes of the above 26 SNPs were detected through Sequenom SNP genotyping assay. Many factors to be considered, including serum levels of alpha-fetoprotein (AFP), TNM staging (AJCC,2010), Karnofsky performance score (KPS), hepatic cirrhosis and surgery, the associations between 26 SNPs with overall survival (OS) in 614 patients with HCC were analyzed by Stastic Analysis System 8.2 (Version 8.2, Cary, NC:SAS Institute Inc, USA).[Results] The age, sex, BMI, The maximum diameter of the tumor, The amount of operative bleeding and postoperative infective rate did not show statistically significant differences. The total length of stays (LOSs), postoperative LOSs and total postoperative hospital costs of study group was significantly less than those of the control group, but the total hospital costs did not show statistically significant difference. Through cost-effectiveness analysis, we found that the patients with using EEN+PN could gain 3000.35 RMB per QALY, while the patients with using TPN could gain 3311.91 RMB per QALY. The incremental cost-effectiveness ratio (ICER, incremental cost/incremental effectiveness, △C/△E) was 583.38 RMB /QALY. The ICER is less than the GDP per capita of China in 2010 (29992 RMB) and the Willing-to-Pay (WTP) (89976 RMB). The stability and reliability of the results of the model were confirmed by sensitivity analysis.Serum levels of alpha-fetoprotein (AFP), TNM staging (AJCC,2010), Karnofsky performance score (KPS), hepatic cirrhosis and surgery have respectively significant associations with OS. Three miRNA-related-SNPs (rs11078662, rs12450517 and rs78312845) were found to have significant correlation with OS. Patients with rs11078662 AG+AA genotype had a significantly longer OS compared than those carrying the GG (HR=0.782,95% CI 0.643-0.950, P=0.0132), as well as rs12450517 AG+AA genotype have improved OS compared with the GG (HR=0.785, 95%CI 0.646-0.955, P=0.0154) and rs78312845 GA+GG genotype have improved OS compared with the AA (HR=0.777,95% CI 0.639-0.946, P=0.0121). The other 23 SNPs have no significant associations with OS.[Conclusions] EEN+PN could partially improve liver function and shorten total hospitalization time. Judging from the view of health economics, EEN+PN is a method of very cost-effectiveness and deserve the clinical expansion.With multi-factors of serum levels of alpha-fetoprotein (AFP), TNM staging (AJCC,2010), Karnofsky performance score (KPS), hepatic cirrhosis and surgery, three miRNA-related-SNPs (rs11078662, rs12450517 and rs78312845) were associated with prognosis of HCC patients.[Objective] The influence of early enteral nutrition (EEN) after surgery is still controversial. The early clinical outcomes and cost-effectiveness of postoperative EEN combined with parenteral nutrition (EEN+PN) in patients with hepatocellular carcinoma (HCC) after hepatectomy were assessed according to four years’clinical experience from a single center.[Methods] A retrospective comparative design of prospectively collected data from January 2010 through December 2013 was undertaken to compare EEN+PN with total parenteral nutrition (TPN) by dividing 379 HCC patients with the score> 3 of Nutritional Risk Screening 2002 (NRS 2002) into two cohorts (142 patients in EEN+PN study group and 237 patients in TPN control group). The early clinical outcomes of different groups were assessed and contrasted. A decision model was developed to compare the economic outcomes between EEN+PN and TPN. We also divided all patients of two groups into two subgroups respectively (centrally located HCC and non-centrally located HCC, cl-HCC and ncl-HCC) by tumor location and investigate their similarities and differences. The uncertainty and robustness of the results of the model were tested by sensitivity analysis.[Results] The age, sex, BMI, The maximum diameter of the tumor. The amount of operative bleeding and postoperative infective rate did not show statistically significant differences. The total length of stays (LOSs), postoperative LOSs and total postoperative hospital costs of study group was significantly less than those of the control group, but the total hospital costs did not show statistically significant difference. Through cost-effectiveness analysis, we found that the patients with using EEN+PN could gain 3000.35 RMB per QALY, while the patients with using TPN could gain 3311.91 RMB per QALY. The incremental cost-effectiveness ratio (ICER, incremental cost/ incremental effectiveness, △C/△E) was 583.38 RMB/QALY. The ICER is less than the GDP per capita of China in 2010 (29992 RMB) and the Willing-to-Pay (WTP) (89976 RMB). The stability and reliability of the results of the model were confirmed by sensitivity analysis.[Conclusions] EEN+PN could partially improve liver function and shorten total hospitalization time. Judging from the view of health economics, EEN+PN is a method of very cost-effectiveness and deserve the clinical expansion.
Keywords/Search Tags:Nutrition support, Hepatocellular carcinoma, Hepatectomy, Cost-effectiveness analysis, Mico-RNA, Single nucleotide polymorphism, Prognosis, Enteral nutrition, Parenteral nutrition, Polymorphism, single nucleotide
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