基于差异共表达识别肝细胞癌患者预后的相关基因  

Identification of prognosis-associated genes in hepatocellular carcinoma patients

作　　者：孙辉[1] 张博文[1] 张明宇[2] Sun Hui Zhang Bowen Zhang Mingyu(Laboratory Center of Pharmacy, College of Pharmacy, Harbin Medical University, HarbinlSO081 , China)

机构地区：[1]哈尔滨医科大学药学院药学实验中心,150081 [2]哈尔滨医科大学药学院药理教研室,150081

出　　处：《国际遗传学杂志》2016年第5期246-253,共8页International Journal of Genetics

摘　　要：目的探索肝细胞癌（ hepatocellular carcinoma, HCC ） 相关基因的表达对患者预后的影响及潜在的作用机制。方法下载TCGA数据库level3水平下的RNASeqV2数据，利用外显子readcount来计算基因的表达。构建差异共表达的基因互作网络，从中提取最大组分。利用CFinder搜索子网。结合多变量Cox风险回归模型和Kaplan—Meier（K—M）生存分析来识别HCC患者预后的相关基因。通过KEGG通路映射来分析相关基因潜在的作用机制。结果识别了17个HCC患者预后相关基因，其中只有FGF9同时参与模块15和模块22两个相关子网（P=5．86E-06，P=1．74E-06）。FGF9恰好处于MAPK信号通路的起始位置，其表达能影响下游Ras信号的传递，进而对细胞的增殖和分化产生影响。结论基因FGF9表达的失调可能会通过影响细胞的增殖和分化功能来影响肝细胞癌患者预后。We aimed to explore the effect of risk gene expression on the prognosis of hepatocellu- lar carcinoma （HCC） patients and the underlying mechanisms. Methods We downloaded RNASeq V2 （level 3 ） data sets from TCGA database, and applied the read count of exons to calculate gene expres- sion. We then built gene interaction network with differential co-expression was constructed and the largest component was extracted. We then applied the CFinder tool to search the closely connected communities. We combined the multivariate Cox regression model with the Kaplan-Meier （K-M） survival analysis to identify prognosis-associated genes of HCC patients. By GO-BP analysis and KEGG pathways mapping, we analyzed the potential mechanism of potential risk genes. Results 17 prognosis- associated genes were identified, of which only FGF9 participated in both the two sub-networks of community 15 and community 22 （P = 5. 86E-06, P = 1.74E-06 ）. FGF9 was present at the initial position of MAPK signal path- way. The expression of FGF9 can regulate the downstream Ras signals, which affects cell proliferation and differentiation. Conclusion The dysregulated gene FGF9 may affect cell proliferation and differentiation, and determine the poor prognosis of HCC patients.

关 键 词：肝细胞癌 预后 差异共表达网络 

分 类 号：R735.7[医药卫生—肿瘤]