CYP27A1基因表达与肝癌患者临床表型相关性及其预后作用瞿兵
Correlation of CYP27A1 expression with the clinical phenotypes of hepatocarcinoma and its prognostic revelance

瞿兵.CYP27A1基因表达与肝癌患者临床表型相关性及其预后作用瞿兵[J].内科急危重症杂志,2017,23(2):

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中文关键词: 肝癌 CYP27A1 临床表型预后

英文关键词:hepatocarcinoma CYP27A1 clinical phenotype prognosis

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作者	单位	E-mail
瞿兵	湖北省恩施土家族苗族自治州民族医院消化内科	15347038186@163.com

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中文摘要:

背景：肝癌是引起肿瘤相关死亡的三大肿瘤之一,其目前临床预后极差。基因表达水平探讨其独立预后因素,将有助于开发新的治疗肝癌靶向药物。方法：本研究通过在GEO数据下载肝癌基因表达数据GSE14520,分析CYP27A1与肝癌患者年龄、性别、 PRMS分类、血清ALT水平、肿瘤大小、结节数目、肝硬化、TNM分期、BCLC分期、CLIP分期以及血清AFP水平等临床表型的相关性,以及CYP27A1与肝癌患者临床预后指标(无进展生存期、总生存期)的关系,明确CYP27A1在对肝癌细胞的作用机制。结果：相较于正常肝脏组织,CYP27A1在肝癌中表达明显下调；CYP27A1高表达组和CYP27A1低表达组患者在年龄和性别分布上无明显差异。两组肝癌患者血清ALT水平及肝硬化情况无明显差异,CYP27A1高表达组患者中PRMS分类、肿瘤大小、肿瘤类型、TNM分期、BCLC分期、CLIP分期、血清AFP水平等临床表型均明显优于CYP27A1低表达组肝癌患者(相应的P值分别为P<0.0001、P=0.003、P=0.071、P=0.01,P=0.007,P=0.004及0.009),CYP27A1高表达组肝癌患者的无进展生存期和总生存期明显优于CYP27A1低表达肝癌患者。CYP27A1可能有丝分裂纺锤体、精子发生、G2M检查点、DNA修复、E2F基因相关分子、MYC基因相关分子、PI3K_AKT_mTOR信号通路以及去折叠蛋白反应等生物学过程影响肝癌细胞增殖。结论：CYP27A1或可作为肝癌患者独立预后因素,高表达CYP27A1的肝癌患者的临床预后明显优越与CYP27A1低表达肝癌患者,基于CYP27A1影响肝癌的具体作用机制有待进一步被证实。

英文摘要:

Background: hepatocarcinoma is one of the three lethal cancers, and the prognosis of patients with hepatocarcinoma remains poor. Investigating the independent prognostic factors of hepatocarcinoma at gene-expression level might facilitate the development of novel agent for treating hepatocarcina. Methods: In the present study, we analyzed the correlation of the expression of CYP27A1 and the characteristics of hepatocarcina patients including age, gender, PRMS classification, ALT, main tumor size, multinodular, cirrhosis, TNM staging, BCLC staging, CLIP staging and AFP. Meanwhile, the progression free survival and overall survival of hepatocarcina patients were also analyzed. Gene set enrichment analysis (GSEA) were conducted to characterize the potential mechanisms regarding the impact of CYP27A1 on hepatocarcina cells. Results: Compared with normal liver tissues, the CYP27A1 was downregulated in tumor cells. No significant differences could be found between CYP27A1 high expression group and CYP27A1 low expression group regarding the age, gender and the serum ALT level of hepatocarcina patients. Patients with higher expression of CYP27A1 turned out to have better PRMS classification, tumor size, tumor type, TNM staging, BCLC staging, CLIP staging and serum AFP level (P<0.0001, P=0.003, P=0.071, P=0.01, P=0.007, P=0.004 and P=0.009), and patients in CYP27A1 high expression group proved to have better progression free survival and overall survival compared with patients in CYP low expression group. Our GSEA results suggested that CYP27A1 might influent the proliferation of hepatocarcinoma through participating the mitotic spindle, spermatogenesis, G2M checkpoint, DNA repair, E2F target, MYC target, PI3K-AKT-mTOR signaling and unfolded protein response. Conclusions: CYP27A1 might be an independent prognostic factor for hepatocarcinoma patients, and patients with higher expression of CYP27A1were proved to have better survival than patients with lower expression of CYP27A1, while the exact mechanisms regarding the impact of CYP27A1 on the hepatocarcinoma remained to be elucidated.