FOXP1 and SPINK1 reflect the risk of cirrhosis progression to HCC with HBV infection
FOXP1 and SPINK1 reflect the risk of cirrhosis progression to HCC with HBV infection
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DOI：
10.1016/j.biopha.2015.04.006
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发表时间：
2015-05-01
影响因子：
7.5
通讯作者：
Xu, Ming-Yi
中科院分区：
文献类型：
--
作者：
Li, Fei;Liu, Ting;Xu, Ming-Yi
背景：肝硬变合并乙肝病毒感染所致的肝细胞癌发病率较高，预后较差。方法：应用Affymetrix基因芯片技术建立基因表达谱，进行基因表达谱分析(SAM)和预测分析(PAM)，筛选15例乙肝病毒(HBVc)相关性肝癌患者癌组织和癌旁组织中的候选标记基因。结果：芯片共筛选出497个差异基因(折叠式变化2；P值0.01)。然后用SAM方法确定162个显著基因(倍数变化-1.46~1.28)。以6.2的阈值验证了一些显示“不良风险标志”的8个基因，这与肝硬变进展为肝细胞癌有关。RT-PCR结果显示，肝癌组和肝硬化组中仅有3个下调和2个上调的预测基因有统计学差异(P值均<0.01)。免疫组化和免疫组化检测发现癌组织中Foxp1和SPINK1蛋白的表达明显高于癌旁组织。结论：Foxp1和SPINK1的过度表达可能参与了乙肝相关性肝硬变的发生发展过程。它们可以作为诊断早期肝细胞癌的潜在生物标志物。(C)2015年爱思唯尔·马森公司。版权所有。
Background: Hepatocellular carcinoma (HCC) deriving from cirrhosis with HBV infection harbors higher morbidity and poor prognosis. The diagnosis of HCC at its early stage is essential for improving the effect of treatment and survival rate of patients.Method: Affymetrix GeneChip was practiced to establish gene expression profile and significance analysis of microarray (SAM) as well as prediction analysis of microarray (PAM) was utilized to screen candidate marker genes in tissue of carcinoma and para-cancerous with cirrhosis from 15 hepatitis B virus (HBV) related HCC patients.Result: Total 497 differential genes were selected by microarray (fold change >2; P value < 0.01). Then 162 significant genes were determined by SAM (fold change -1.46 to 1.28). A number of 8-genes showing "poor risk signature" was validated with threshold of 6.2, which was associated with cirrhosis progressing to HCC. Only 3 down-regulated and 2 up-regulated predictor genes had statistical difference in HCC and cirrhosis groups by RT-PCR (P value < 0.01). Forkhead box protein 1 (FOXP1) and serine protease inhibitor Kazal-type 1 (SPINK1) proteins were found significantly increased in carcinoma tissues than para-cancerous cirrhotic tissues by IH and WB.Conclusion: Over-expression of FOXP1 and SPINK1 may participate in the carcinogenesis of HBV related cirrhosis. They could use as potential biomarkers for diagnosing early HCC. (C) 2015 Elsevier Masson SAS. All rights reserved.