切换至 "中华医学电子期刊资源库"
高级检索
中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2018, Vol. 07 ›› Issue (01) : 73 -76. doi: 10.3877/cma.j.issn.2095-3232.2018.01.018

所属专题： 文献；

基础研究

载脂蛋白F在肝细胞癌患者生存预后中的临床意义
周伯宣1, 姚志成2, 熊志勇2, 李瑞曦1, 代天星1, 许明星1, 范伟明1, 周正1, 梁豪1, 邓美海1, 凌云彪1,†()   
  1. 1. 510630　广州，中山大学附属第三医院肝胆外科
    2. 510630　广州，中山大学附属第三医院普通外科
  • 收稿日期:2017-11-07 出版日期:2018-02-10
  • 通信作者: 凌云彪
  • 基金资助:
    国家自然科学基金(81470860); 广东省科技计划项目(2012A020602002)

Clinical significance of apolipoprotein F in prognosis of patients with hepatocellular carcinoma

Boxuan Zhou1, Zhicheng Yao2, Zhiyong Xiong2, Ruixi Li1, Tianxing Dai1, Mingxing Xu1, Weiming Fan1, Zheng Zhou1, Hao Liang1, Meihai Deng1, Yunbiao Ling1,†()   

  1. 1. Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
    2. General Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2017-11-07 Published:2018-02-10
  • Corresponding author: Yunbiao Ling
  • About author:
    Corresponding author: Ling Yunbiao, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

周伯宣, 姚志成, 熊志勇, 李瑞曦, 代天星, 许明星, 范伟明, 周正, 梁豪, 邓美海, 凌云彪. 载脂蛋白F在肝细胞癌患者生存预后中的临床意义[J/OL]. 中华肝脏外科手术学电子杂志, 2018, 07(01): 73-76.

Boxuan Zhou, Zhicheng Yao, Zhiyong Xiong, Ruixi Li, Tianxing Dai, Mingxing Xu, Weiming Fan, Zheng Zhou, Hao Liang, Meihai Deng, Yunbiao Ling. Clinical significance of apolipoprotein F in prognosis of patients with hepatocellular carcinoma[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2018, 07(01): 73-76.

目的

探讨载脂蛋白（Apo）F在肝细胞癌(肝癌)中的表达及其在患者生存预后中的应用价值。

方法

50例肝癌标本取自2015年9月至2016年9月在中山大学附属第三医院手术切除患者，且均经术后病理学检查证实。患者均签署知情同意书，符合医学伦理学规定。其中男37例，女13例；年龄31～67岁，中位年龄53岁。采用RT-PCR法检测肝癌组织ApoF mRNA的表达情况。利用基因表达汇编（GEO）数据库，对表达谱资料进行分析。两组ApoF表达量比较采用t检验，临床相关指标的相关性分析采用χ2检验，生存预后分析采用Kaplan-Meier法和Log rank检验。

结果

肝癌组织ApoF mRNA平均相对表达量为0.15±0.07，明显低于癌旁组织的0.55±0.09（t=-6.26，P<0.05）。GEO在线分析显示ApoF表达与患者肝硬化状态明显相关，合并肝硬化的肝癌患者多伴有ApoF低表达（χ2=4.626，P<0.05)。ApoF高表达组和低表达组患者5年无瘤生存率分别为55.9%、32.0%，差异有统计学意义（χ2=3.939，P<0.05)。

结论

肝癌组织中存在ApoF低表达，ApoF低表达与患者肝硬化状态有关。ApoF低表达患者预后较差，ApoF具有抑癌作用。

关键词: 癌，肝细胞, 载脂蛋白类, 预后
Objective

To investigate the expression of apolipoprotein (Apo) F in hepatocellular carcinoma (HCC) and its application value in the prognosis of patients with HCC.

Methods

50 HCC samples were procured from patients undergoing surgical resection in the Third Affiliated Hospital of Sun Yat-sen University between September 2015 and September 2016, and all the samples were confirmed by postoperative pathological examination. The informed consents of all patients were obtained and the local ethical committee approval was received. There were 37 males and 13 females, aged from 31-67 with a median age of 53 years old. The expression of ApoF mRNA in HCC tissues was detected by RT-PCR. The expression profile was analyzed by using data from the Gene Expression Omnibus (GEO). The expression of ApoF between two groups were compared by t test. Correlation analysis of clinical related parameter was conducted by Chi-square test, and survival prognosis was analyzed by Kaplan-Meier test and Log rank test.

Results

The average relative expression of ApoF mRNA in HCC tissues was 0.15±0.07, significantly lower than 0.55±0.09 in the adjacent tissues (t=-6.26, P<0.05). GEO online analysis showed that expression of ApoF was significantly correlated with the status of liver cirrhosis, and most HCC patients with liver cirrhosis presented low expression of ApoF (χ2=4.626, P<0.05). The 5-year disease-free survival was respectively 55.9% and 32.0% in ApoF high expression group and low expression group, where significant difference was observed (χ2=3.939, P<0.05).

Conclusions

Low expression of ApoF exists in HCC tissues, and it is related to the liver cirrhosis status of patients. Patients with low ApoF expression present poorer prognosis. ApoF plays a role in inhibiting the cancer.

Key words: Carcinoma, hepatocellular, Apolipoproteins, Prognosis
表1 ApoF表达水平与肝癌患者临床病理学参数关系
参数 例数 高表达 低表达 χ2值 P值
年龄（岁） ? ? ? 1.918 0.166
? ≤55 166 78 88 ? ?
? >55 76 43 33 ? ?
性别 ? ? ? 0.353 0.553
? 男 213 105 108 ? ?
? 女 29 16 13 ? ?
ALT（U/L） ? ? ? 0.273 0.602
? ≤50 142 73 69 ? ?
? >50 100 48 52 ? ?
AFP（μg/L） ? ? ? 0.410 0.522
? ≤200 128 67 61 ? ?
? >200 114 54 60 ? ?
肝硬化 ? ? ? 4.626 0.031
? 无 19 14 5 ? ?
? 有 223 107 116 ? ?
肿瘤直径（cm） ? ? ? 0.568 0.451
? <5 153 74 79 ? ?
? ≥5 89 47 42 ? ?
肿瘤数目 ? ? ? 0.098 0.754
? 单个 190 96 94 ? ?
? 多发 52 25 27 ? ?
AJCC T分期 ? ? ? 0.595 0.743
? T1 96 45 51 ? ?
? T2 78 41 37 ? ?
? T3 68 35 33 ? ?
BCLC分期 ? ? ? 2.102 0.552
? 0 37 22 15 ? ?
? A 152 74 78 ? ?
? B 24 11 13 ? ?
? C 29 14 15 ? ?
CLIP分期 ? ? ? 2.548 0.280
? 0 98 54 44 ? ?
? 1 79 34 45 ? ?
? 2,3,4,5 65 33 32 ? ?
PRMS分级 ? ? ? 2.000 0.157
? 高 121 66 55 ? ?
? 低 121 55 66 ? ?
图1 ApoF高、低表达组肝癌患者生存预后Kaplan-Meier生存曲线图
[1]
Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma[J]. Lancet, 2012, 379(9822):1245-1255.
[2]
Pogribny IP, Rusyn I. Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma[J]. Cancer Lett, 2014, 342(2):223-230.
[3]
Muir K, Hazim A, He Y, et al. Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma[J]. Cancer Res, 2013, 73(15):4722-4731.
[4]
Yamashita T, Honda M, Takatori H, et al. Activation of lipogenic pathway correlates with cell proliferation and poor prognosis in hepatocellular carcinoma[J]. J Hepatol, 2009, 50(1):100-110.
[5]
Lagor WR, Fields DW, Khetarpal SA, et al. The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice[J]. PLoS One, 2012, 7(2):e31616.
[6]
Lagor WR, Brown RJ, Toh SA, et al. Overexpression of apolipoprotein F reduces HDL cholesterol levels in vivo[J]. Arterioscler Thromb Vasc Biol, 2009, 29(1):40-46.
[7]
Shen XB, Huang L, Zhang SH, et al. Transcriptional regulation of the apolipoprotein F (ApoF) gene by ETS and C/EBPα in hepatoma cells[J]. Biochimie, 2015(112):1-9.
[8]
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation[J]. Science, 2009, 324(5930):1029-1033.
[9]
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, et al. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation[J]. Cell Metab, 2008, 7(1):11-20.
[10]
Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism[J]. Nat Rev Cancer, 2011, 11(2):85-95.
[11]
Kim J, DeBerardinis RJ. Blocking fatty acid synthesis reduces lung tumor growth in mice[J]. Nat Med, 2016, 22(10):1077-1078.
[12]
Rysman E, Brusselmans K, Scheys K, et al. De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation[J]. Cancer Res, 2010, 70(20):8117-8126.
[13]
Jiang J, Zhang X, Wu C, et al. Increased plasma apoM levels in the patients suffered from hepatocellular carcinoma and other chronic liver diseases[J]. Lipids Health Dis, 2008(7):25.
[14]
Yokoyama Y, Kuramitsu Y, Takashima M, et al. Protein level of apolipoprotein E increased in human hepatocellular carcinoma[J]. Int J Oncol, 2006, 28(3):625-631.
[15]
Ma XL, Gao XH, Gong ZJ, et al. Apolipoprotein A1: a novel serum biomarker for predicting the prognosis of hepatocellular carcinoma after curative resection[J]. Oncotarget, 2016, 7(43):70654-70668.
[16]
Shi J, Yang H, Duan X, et al. Apolipoproteins as differentiating and predictive markers for assessing clinical outcomes in patients with small cell lung cancer[J]. Yonsei Med J, 2016, 57(3):549-556.
[17]
Morton RE, Greene DJ. Conversion of lipid transfer inhibitor protein (apolipoprotein F) to its active form depends on LDL composition[J]. J Lipid Res, 2011, 52(12):2262-2271.
[18]
Peloso GM, Demissie S, Collins D, et al. Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease[J]. J Lipid Res, 2010, 51(12):3524-3532.
[19]
He Y, Greene DJ, Kinter M, et al. Control of cholesteryl ester transfer protein activity by sequestration of lipid transfer inhibitor protein in an inactive complex[J]. J Lipid Res, 2008, 49(7):1529-1537.
[1] 张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[2] 许杰, 李亚俊, 韩军伟. 两种入路下腹腔镜根治性全胃切除术治疗超重胃癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 19-22.
[3] 李华志, 曹广, 刘殿刚, 张雅静. 不同入路下行肝切除术治疗原发性肝细胞癌的临床对比[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 52-55.
[4] 常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[5] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[6] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[7] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[8] 顾雯, 凌守鑫, 唐海利, 甘雪梅. 两种不同手术入路在甲状腺乳头状癌患者开放性根治性术中的应用比较[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 687-690.
[9] 付成旺, 杨大刚, 王榕, 李福堂. 营养与炎症指标在可切除胰腺癌中的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 704-708.
[10] 梁孟杰, 朱欢欢, 王行舟, 江航, 艾世超, 孙锋, 宋鹏, 王萌, 刘颂, 夏雪峰, 杜峻峰, 傅双, 陆晓峰, 沈晓菲, 管文贤. 联合免疫治疗的胃癌转化治疗患者预后及术后并发症分析[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 619-623.
[11] 刘郁, 段绍斌, 丁志翔, 史志涛. miR-34a-5p 在结肠癌患者的表达及其与临床特征及预后的相关性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 485-490.
[12] 陈倩倩, 袁晨, 刘基, 尹婷婷. 多层螺旋CT 参数、癌胚抗原、错配修复基因及病理指标对结直肠癌预后的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 507-511.
[13] 曾明芬, 王艳. 急性胰腺炎合并脂肪肝患者CT 与彩色多普勒超声诊断参数与其病情和预后的关联性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 531-535.
[14] 沈炎, 张俊峰, 唐春芳. 预后营养指数结合血清降钙素原、胱抑素C及视黄醇结合蛋白对急性胰腺炎并发急性肾损伤的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 536-540.
[15] 王景明, 王磊, 许小多, 邢文强, 张兆岩, 黄伟敏. 腰椎椎旁肌的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 846-852.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号

AI
小
编
AI小编
你好！我是《中华医学电子期刊资源库》AI小编，有什么可以帮您的吗？