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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 ›› 2021, Vol. 10 ›› Issue (02) : 210 -214. doi: 10.3877/cma.j.issn.2095-3232.2021.02.019

所属专题： 文献；

基础研究

生长激素受体与肝细胞癌增殖迁移及预后的关系
钟昭众1, 熊志勇1, 梁豪1, 袁峰1, 曹明波1, 向莎1, 邓美海1,†()   
  1. 1. 510630　广州，中山大学附属第三医院肝胆外科
  • 收稿日期:2021-01-04 出版日期:2021-04-10
  • 通信作者: 邓美海
  • 基金资助:
    广东省自然科学基金(2016A030313848)

Relationship between growth hormone receptor and proliferation, migration and clinical prognosis of hepatocellular carcinoma

Zhaozhong Zhong1, Zhiyong Xiong1, Hao Liang1, Feng Yuan1, Mingbo Cao1, Sha Xiang1, Meihai Deng1,†()   

  1. 1. Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2021-01-04 Published:2021-04-10
  • Corresponding author: Meihai Deng
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引用本文：

钟昭众, 熊志勇, 梁豪, 袁峰, 曹明波, 向莎, 邓美海. 生长激素受体与肝细胞癌增殖迁移及预后的关系[J]. 中华肝脏外科手术学电子杂志, 2021, 10(02): 210-214.

Zhaozhong Zhong, Zhiyong Xiong, Hao Liang, Feng Yuan, Mingbo Cao, Sha Xiang, Meihai Deng. Relationship between growth hormone receptor and proliferation, migration and clinical prognosis of hepatocellular carcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(02): 210-214.

目的

探讨生长激素受体（GHR）在肝细胞癌（HCC）中表达及其对HCC细胞增殖、迁移能力及患者预后的影响。

方法

从癌症基因组图谱（TCGA）公共数据库下载HCC的RNA表达谱数据和临床信息，比较HCC组织和癌旁组织GHR mRNA表达。根据GHR表达高低绘制Kaplan-Meier生存曲线，生存分析采用Log-rank检验。qRT-PCR检测30例HCC组织和癌旁组织GHR mRNA表达。采用siRNA技术沉默HCC细胞中的GHR基因，EdU法检测siRNA组和对照组肝癌细胞的增殖能力，划痕实验观察两组细胞的迁移能力。GHR mRNA表达等数据比较采用t 检验。

结果

TCGA数据库分析发现，HCC组织中GHR mRNA的平均相对表达量为17.22±0.09，明显低于癌旁组织的20.26±0.12（t=-11.95，P<0.05）。30例HCC的GHR mRNA相对表达量为125.40±70.70，明显低于癌旁组织的610.20±167.73（t=-5.53，P<0.05）。生存分析显示，GHR高表达组患者的总体生存预后更好（HR=0.56，P<0.05）。97L细胞转染siRNA后，siRNA组GHR mRNA相对表达量为0.012 1±0.002 5，明显低于对照组的1.000 0（t=-1 342.00，P<0.05）。EdU增殖实验显示，siRNA组增殖期细胞百分率为（46.20±0.10）%，明显高于对照组的（32.50±0.04）%（t=5.36，P<0.05）。细胞划痕实验显示，沉默GHR基因后细胞的侵袭转移能力增强。

结论

GHR在HCC中低表达，GHR表达与HCC患者预后相关，低表达患者预后差。抑制GHR表达可促进HCC细胞增殖和迁移。

关键词: 癌, 肝细胞, 生长激素受体, 细胞增殖, 细胞迁移, 预后
Objective

To investigate the expression level of growth hormone receptor (GHR) in hepatocellular carcinoma (HCC) and its effect on the proliferation, migration of HCC cells and the clinical prognosis of HCC patients.

Methods

The RNA expression profile and clinical data of HCC were downloaded from the public database the Cancer Genome Atlas (TCGA), and the expression levels of GHR mRNA were compared between HCC and adjacent tissues. The survival curve was delineated by Kaplan-Meier method according to GHR expression level. The survival analysis was conducted by Log-rank test. The expression of GHR mRNA in 30 paired HCC and adjacent tissues were detected by qRT-PCR. The GHR gene in HCC cells was silenced by siRNA. The proliferation ability of HCC cells in siRNA and control groups was detected by EdU proliferation assay. The migration ability of HCC cells in two groups was observed by cell scratch test. GHR mRNA expression and other data were statistically compared by t test.

Results

The TCGA database analysis demonstrated that the average relative expression level of GHR mRNA in HCC tissues was 17.22±0.09, significantly lower than 20.26±0.12 in adjacent tissues (t=-11.95, P<0.05). The relative expression of GHR mRNA in 30 HCC tissues was 125.40±70.70, significantly lower than 610.20±167.73 in adjacent tissues (t=-5.53, P<0.05). Survival analysis showed that patients with high expression of GHR had better overall survival and prognosis (HR=0.56, P<0.05). After 97L cells were transfected with siRNA, the relative expression of GHR mRNA in siRNA group was 0.012 1±0.002 5, significantly lower than 1.000 0 in control group (t=-1 342.00, P<0.05). EdU proliferation assay showed that the percentage of cells in proliferation phase in siRNA group was (46.20±0.10)%, significantly higher than (32.50±0.04)% in the control group (t=5.36, P<0.05). Cell scratch test revealed that the invasion and metastasis abilities of cells enhanced after silencing the GHR gene.

Conclusions

The expression level of GHR is low in HCC, which is associated with the clinical prognosis of HCC patients. HCC patients with low expression of GHR has poorer prognosis. Inhibiting GHR expression promotes the proliferation and migration of HCC cells.

Key words: Carcinoma, hepatocellular, Growth hormone receptor, Cell proliferation, Cell migration, Prognosis
图1 肝细胞癌患者GHR表达与预后关系的Kaplan-Meier生存曲线
图2 倒置显微镜下观察97L肝癌细胞划痕实验（×100）
[1]
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[2]
Yang JD, Hainaut P, Gores GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(10):589-604.
[3]
Pascual S, Herrera I, Irurzun J. New advances in hepatocellular carcinoma[J]. World J Hepatol, 2016, 8(9):421-438.
[4]
Dehkhoda F, Lee CMM, Medina J, et al. The growth hormone receptor: mechanism of receptor activation, cell signaling, and physiological aspects[J]. Front Endocrinol, 2018(9):35.
[5]
Bergan-Roller HE, Sheridan MA. The growth hormone signaling system: insights into coordinating the anabolic and catabolic actions of growth hormone[J]. Gen Comp Endocrinol, 2018(258):119-133.
[6]
Perry JK, Emerald BS, Mertani HC, et al. The oncogenic potential of growth hormone[J]. Growth Horm IGF Res, 2006, 16(5/6):277-289.
[7]
Wu ZS, Yang K, Wan Y, et al. Tumor expression of human growth hormone and human prolactin predict a worse survival outcome in patients with mammary or endometrial carcinoma[J]. J Clin Endocrinol Metab, 2011, 96(10):E1619-1629.
[8]
Chesnokova V, Zonis S, Zhou C, et al. Growth hormone is permissive for neoplastic colon growth[J]. Proc Natl Acad Sci U S A, 2016, 113(23):E3250-3259.
[9]
Lango Allen H, Estrada K, Lettre G, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height[J]. Nature, 2010, 467(7317):832-838.
[10]
Cheng M, Huang W, Cai W, et al. Growth hormone receptor promotes osteosarcoma cell growth and metastases[J]. FEBS Open Bio, 2020, 10(1):127-134.
[11]
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[12]
Guevara-Aguirre J, Guevara A, Palacios I, et al. GH and GHR signaling in human disease[J]. Growth Horm IGF Res, 2018(38):34-38.
[13]
Chhabra Y, Waters MJ, Brooks AJ. Role of the growth hormone-IGF-1 axis in cancer[J]. Expert Rev Endocrinol Metab, 2011, 6(1): 71-84.
[14]
Brunet-Dunand SE, Vouyovitch C, Araneda S, et al. Autocrine human growth hormone promotes tumor angiogenesis in mammary carcinoma[J]. Endocrinology, 2009, 150(3):1341-1352.
[15]
Basu R, Wu S, Kopchick JJ. Targeting growth hormone receptor in human melanoma cells attenuates tumor progression and epithelial mesenchymal transition via suppression of multiple oncogenic pathways[J]. Oncotarget, 2017, 8(13):21579-21598.
[16]
Conway-Campbell BL, Wooh JW, Brooks AJ, et al. Nuclear targeting of the growth hormone receptor results in dysregulation of cell proliferation and tumorigenesis[J]. Proc Natl Acad Sci U S A, 2007, 104(33):13331-13336.
[17]
Niimi S, Hayakawa T, Tanaka A. Hormonal regulation of growth hormone receptors in primary cultured rat hepatocytes[J]. Endocrinology, 1990, 127(2):688-694.
[18]
Katz TA, Grimm SL, Kaushal A, et al. Hepatic tumor formation in adult mice developmentally exposed to organotin[J]. Environ Health Perspect, 2020, 128(1):17010.
[19]
Cao J, Luo SM, Liang L, et al. Effects of parenteral nutrition without and with growth hormone on growth hormone/insulin-like growth factor-1 axis after hepatectomy in hepatocellular carcinoma with liver cirrhosis[J]. JPEN J Parenter Enteral Nutr, 2007, 31(6):496-501.
[20]
Berman RS, Harrison LE, Pearlstone DB, et al. Growth hormone, alone and in combination with insulin, increases whole body and skeletal muscle protein kinetics in cancer patients after surgery[J]. Ann Surg, 1999, 229(1):1-10.
[21]
Luo SM, Liang LJ, Lai JM. Effects of recombinant human growth hormone on remnant liver after hepatectomy in hepatocellular carcinoma with cirrhosis[J]. World J Gastroenterol, 2004, 10(9):1292-1296.
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