ABSTRACT
The aim of our study was to determine the impact of genetic polymorphisms in the caspase (CASP) genes on prognosis of hepatocellular carcinoma (HCC). We genotyped 7 potentially functional polymorphisms in CASP3, CASP7, CASP8, CASP9, CASP10 genes in 362 HCC patients of receiving surgical resection of HCC tumor. The associations of genotype and haplotype with overall survival (OS) and disease free survival (DFS) were analyzed by using the Cox proportional hazards model. We found that the CASP9 rs4645981 C allele was significantly associated with positive effect on DFS (P = 0.011 and 0.016 for CT+CC vs. TT in univariate and multivariate analysis, respectively), CT genotype was associated with a better OS of HCC than the TT genotype both in univariate and multivariate analysis (P = 0.048 and 0.041, respectively). Moreover, the CASP3 rs2705897 GT genotype showed marginally significant association with decreased OS and DFS, compared with the GG genotype. One haplotype TT/TG in CASP3 (constructed by rs12108497 T>C and rs2705897 T>G) was significantly associated with decreased OS and DFS, compared to the common haplotype TT/TT both in univariate analysis (P = 0.021 and 0.026, respectively) and multivariate analysis (P = 0.025 and 0.030, respectively). The haplotype GT/GT in CASP9 (constructed by rs4645978 A>G and rs4645981 C>T) was significantly associated with decreased DFS both in univariate and multivariate analysis (P = 0.012 and 0.010, respectively). In conclusion, the CASP9 rs4645981 polymorphism, CASP3 and CASP9 haplotypes may be useful prognosis markers for HCC patients with surgical resection of tumor.
Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/surgery , Caspases/genetics , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Polymorphism, Single Nucleotide , Asian People/genetics , Carcinoma, Hepatocellular/pathology , China , Disease-Free Survival , Female , Genetic Predisposition to Disease , Genotyping Techniques , Haplotypes , Humans , Kaplan-Meier Estimate , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Tumor BurdenABSTRACT
To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).
Subject(s)
Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/genetics , HLA-DQ Antigens/genetics , Hepatitis B/complications , Liver Neoplasms/complications , Liver Neoplasms/genetics , STAT4 Transcription Factor/genetics , Carcinoma, Hepatocellular/virology , Gene Expression , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Hepatitis B/virology , Hepatitis B virus/genetics , Humans , Liver Neoplasms/virology , Polymorphism, Single NucleotideABSTRACT
AIM: To develop a method to deliver mesenchymal stem cells (MSCs) into the pleural cavity for the treatment of pleural diseases. METHODS: MSCs were isolated from rat bone marrow of rats and labeled with 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) or green fluorescent protein (GFP) using a lentiviral vector. Eighteen Sprague-Dawley (SD) rats were inoculated intrapleurally with 1×10(6) MSCs-DAPI. The distribution of the fluorescent cells was observed using fluorescent microscopy for the following 30 d. Another 12 rats inoculated intrapleurally with 1×10(6) MSCs-GFP were observed for 14 d. RESULTS: The isolated cells were typical MSC phenotypes and could differentiate into adipocytes, osteoblasts, and chondroblasts in vitro. Microscopic analysis revealed that the labeled cells adhered to the surface of the pleural cavity. The highest number of the labeled cells was found to be adhered to all specimens from the mediastinal pleura, but no labeled cells were detected in the lung parenchyma or other tissues/organs, such as the liver, kidney, spleen, and mesenterium. Incidentally, stomas were found in the mediastinal pleura. The recovered MSCs-GFP from the pleural cavity retained their ability to adhere and proliferate. CONCLUSION: We have established a novel method for intrapleural delivery of MSCs. The distribution of intrapleurally delivered MSCs was found to be limited to the pleurae and the pleural cavity, thereby providing us with a new approach to further investigation of the therapeutic roles of MSCs in pleural diseases.
