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中华临床医师杂志(电子版)

中华临床医师杂志(电子版) ›› 2020, Vol. 14 ›› Issue (06) : 401 -406. doi: 10.3877/cma.j.issn.1674-0785.2020.06.001

所属专题： 文献；

临床研究

谷胱甘肽过氧化物酶2在肺腺癌中的表达及临床意义
焦南林1, 陈碧2, 张有为3, 孙三元3,†()   
  1. 1. 241001　安徽芜湖，皖南医学院弋矶山医院病理科
    2. 221002　徐州医科大学附属医院呼吸科
    3. 221009　徐州市中心医院肿瘤内科
  • 收稿日期:2020-01-17 出版日期:2020-06-15
  • 通信作者: 孙三元
  • 基金资助:
    国家自然科学基金面上项目(81973346)

Clinical significance of expression of glutathione peroxidase 2 in lung adenocarcinoma

Nanlin Jiao1, Bi Chen2, Youwei Zhang3, Sanyuan Sun3,†()   

  1. 1. Department of Pathology, Yijishan Hospital of Wannan Medical College, Wuhu 241001, China
    2. Department of Respiratory Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
    3. Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou 221009, China
  • Received:2020-01-17 Published:2020-06-15
  • Corresponding author: Sanyuan Sun
  • About author:
    Corresponding author: Sun Sanyuan, Email:
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焦南林, 陈碧, 张有为, 孙三元. 谷胱甘肽过氧化物酶2在肺腺癌中的表达及临床意义[J]. 中华临床医师杂志(电子版), 2020, 14(06): 401-406.

Nanlin Jiao, Bi Chen, Youwei Zhang, Sanyuan Sun. Clinical significance of expression of glutathione peroxidase 2 in lung adenocarcinoma[J]. Chinese Journal of Clinicians(Electronic Edition), 2020, 14(06): 401-406.

目的

探讨谷胱甘肽过氧化物酶2（GPX2）在肺腺癌中的表达及临床意义。

方法

收集皖南医学院弋矶山医院病理科和徐州市中心医院病理科2010年1月至2013年12月存档的152例原发性肺腺癌及其癌旁正常组织标本蜡块。标本行免疫组织化学检测GPX2与ATP结合盒转运蛋白（ABCB6）在肺腺癌组织中的表达。正电子发射计算机断层成像（PET/CT）结果由患者术前检查获得。利用在线工具GEPIA、cBioPortal分析GPX2 mRNA在肺腺癌组织的表达。采用采取t检验比较GPX2表达量和18F-FDG的最大化标准摄取值在肺癌组织和正常组织的差异，采用Pearson相关性分析分析GPX2与ABCB6蛋白表达的相关性，采取χ2检验比较GPX2蛋白表达在不同临床病理特征之间的差异，同时应用Kaplan-Meier法分析肺腺癌患者的生存预后。

结果

基于TCGA和GTEx数据，GPX2 mRNA在肺腺癌组织（483例）的表达较正常组织（347例）明显升高，且与ABCB6表达水平呈正相关（r=0.57，P<0.001）。在本研究的样本中，89例（58.6%）肺腺癌组织的GPX2蛋白表达较正常组织升高（P<0.001），同样，GPX2与ABCB6蛋白表达水平正相关（r=0.697，P<0.001）；其中，GPX2高表达患者（29例）的18F-FDG的最大化标准摄取值也高于GPX2低表达患者（26例），差异具有统计学意义（t=4.262，P<0.001）。虽然GPX2蛋白表达在不同临床病理特征之间的差异均无统计学意义（P>0.05），但是GPX2表达升高的患者较GPX2低表达患者无进展生存期减少［平均34.75个月（95%CI：29.746~39.747） vs 48.91个月（95%CI： 41.033~56.779），P=0.009］。

结论

GPX2在肺腺癌发挥癌基因作用，其作用机制可能与ABCB6介导的糖酵解有关。

关键词: 腺癌，肺, 谷胱甘肽过氧化物酶, ATP结合盒转运蛋白, 正电子发射计算机断层显像, 预后
Objective

To explore the significance of expression of glutathione peroxidase 2 (GPX2) in lung adenocarcinoma (LUAD).

Methods

One hundred and fifty-two cases of primary LUAD and matched paracancerous tissue samples were collected from January 2010 to December 2013 at the Department of Pathology of Yijishan Hospital of Wannan Medical College and the Department of Pathology of Xuzhou Central Hospital. Immunohistochemistry was used to detect the protein expression of GPX2 and ATP binding cassette subfamily B member 6 (ABCB6). Positron emission tomography/computed tomography (PET/CT) was performed preoperatively. The expression of GPX2 mRNA in LUAD tissues was analyzed online with GEPIA and cBioPortal tools. The t-test was used to compare the difference between GPX2 expression and maximum standardized uptake value (SUV) of 18-fluorodeoxyglucose (18F-FDG) in lung cancer tissues and normal tissues, Pearson correlation analysis was performed to analyze the correlation between GPX2 expression and ABCB6 protein expression, the χ2-test was used to compare the difference between different clinicopathological features, and Kaplan-Meier method was used to analyze the survival prognosis of lung adenocarcinoma patients.

Results

Based on the TCGA and GTEx data, GPX2 mRNA expression was upregulated in LUAD tissues (n=483) compared with that in normal tissues (n=347), and it was positively correlated with ABCB6 mRNA expression (r=0.57, P<0.001). In our cohort, there were 89 (58.6%) cases showing a higher level of GPX2 protein expression in tumor tissues than in adjacent normal tissues (P<0.001). Also, GPX2 protein expression was positively correlated with ABCB6 expression (r=0.697, P<0.001). Furthermore, the maximum SUV of 18F-FDG was higher in the GPX2 high expression group (n=29) than in the GPX2 low expression group (n=26). Although there were no correlations between GPX2 expression and patients′ clinicopathological features, LUAD patients with elevated GPX2 expression had a shorter disease-free survival (DFS) than those with low GPX2 expression [mean 34.75 (95%CI: 29.746-39.747) months vs 48.91 (95%CI: 41.033-56.779) months, P=0.009].

Conclusion

GPX2 acts as an oncogene in LUAD and promotes LUAD progression by regulating ABCB6-mediated glycolysis.

Key words: Adenocarcinoma, lung, Glutathione peroxidase, ATP binding cassette subfamily B member 6, Positron emission tomography/computed tomography, Prognosis
图1 GPX2与ABCB6表达情况　图a为GEPIA在线工具分析肺腺癌与正常组织GPX2 mRNA表达水平；图b为cBioPortal在线工具分析GPX2与ABCB6 mRNA的关系；图c为本研究样本GPX2与ABCB6蛋白表达的关系；图d为不同GPX2表达量在18F-FDG SUVmax上的差异
图2 肺腺癌患者GPX2、ABCB6蛋白表达（×200）与PET/CT结果的典型对照　病例1 GPX2与ABCB6均为高表达（连续切片），最大化标准摄取值值较高；病例2 GPX2低表达，ABCB6中表达（连续切片），最大化标准摄取值值较低
表1 GPX2蛋白表达与肺腺癌临床病理特征的关系（例）
病理因素 例数 高/中表达 低表达 χ2值 P值
性别 ? ? ? 0.547 0.460
? 男 85 52 33 ? ?
? 女 67 37 30 ? ?
年龄（岁） ? ? ? 0.269 0.604
? <60 71 40 31 ? ?
? ≥60 81 49 32 ? ?
肿瘤大小（cm） ? ? ? 0.344 0.557
? >3 67 41 26 ? ?
? ≤3 85 48 37 ? ?
分化程度 ? ? ? 1.703 0.192
? 好/中 102 56 46 ? ?
? 差 50 33 17 ? ?
淋巴结转移 ? ? ? 1.280 0.258
? 无 81 44 37 ? ?
? 有 71 45 26 ? ?
TNM分期 ? ? ? 1.596 0.206
? Ⅰ/Ⅱ 68 36 32 ? ?
? Ⅲ/Ⅳ 84 53 31 ? ?
图3 GPX2表达与肺腺癌预后　图a为GEPIA在线工具分析GPX2 mRNA表达与总生存率的关系；图b为本研究选取的样本中，不同GPX2蛋白表达水平患者总生存率的差异，图c为不同GPX2蛋白表达水平患者无进展生存率的差异；GPX2为谷胱甘肽过氧化物酶2
1
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015 [J]. CA Cancer J Clin, 2016, 66(2): 115-132.
2
杜凤华，闵旭红，梅晓冬. 肺腺癌靶向治疗药物的应用及耐药机制 [J]. 临床肺科杂志, 2018, 23(1): 168-172.
3
Brigelius-Flohé R, Maiorino M. Glutathione peroxidases [J]. Biochim Biophys Acta, 2013, 1830(5): 3289-3303.
4
Kipp AP. Selenium-Dependent Glutathione Peroxidases During Tumor Development [J]. Adv Cancer Res, 2017, 136: 109-138.
5
Brigelius-Flohé R, Kipp AP. Physiological functions of GPx2 and its role in inflammation-triggered carcinogenesis [J]. Ann N Y Acad Sci, 2012, 1259: 19-25.
6
Naiki-Ito A, Asamoto M, Hokaiwado N, et al. Gpx2 is an overexpressed gene in rat breast cancers induced by three different chemical carcinogens [J]. Cancer Res, 2007, 67(23): 11353-11358.
7
Liu T, Kan XF, Ma C, et al. GPX2 overexpression indicates poor prognosis in patients with hepatocellular carcinoma [J]. Tumour Biol, 2017, 39(6): 1010428317700410.
8
Liu C, He X, Wu X, et al. Clinicopathological and prognostic significance of GPx2 protein expression in nasopharyngeal carcinoma [J]. Cancer Biomark, 2017, 19(3): 335-340.
9
Lei Z, Tian D, Zhang C, et al. Clinicopathological and prognostic significance of GPX2 protein expression in esophageal squamous cell carcinoma [J]. BMC Cancer, 2016, 16: 410.
10
Liu D, Sun L, Tong J, et al. Prognostic significance of glutathione peroxidase 2 in gastric carcinoma [J]. Tumour Biol, 2017, 39(6): 1010428317701443.
11
Murawaki Y, Tsuchiya H, Kanbe T, et al. Aberrant expression of selenoproteins in the progression of colorectal cancer [J]. Cancer Lett, 2008, 259(2): 218-230.
12
Liu K, Jin M, Xiao L, et al. Distinct prognostic values of mRNA expression of glutathione peroxidases in non-small cell lung cancer [J]. Cancer Manag Res, 2018, 10: 2997-3005.
13
Barrera LN, Cassidy A, Wang W, et al. TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death [J]. Biochim Biophys Acta, 2012, 1823(10): 1914-1924.
14
Naiki T, Naiki-Ito A, Iida K, et al. GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis [J]. Oncotarget, 2018, 9(22): 15847-15859.
15
Emmink BL, Laoukili J, Kipp AP, et al. GPx2 suppression of H2O2 stress links the formation of differentiated tumor mass to metastatic capacity in colorectal cancer [J]. Cancer Res, 2014, 74(22): 6717-6730.
16
Naiki T, Naiki-Ito A, Asamoto M, et al. GPX2 overexpression is involved in cell proliferation and prognosis of castration-resistant prostate cancer [J]. Carcinogenesis, 2014, 35(9): 1962-1967.
17
Moreno Leon L, Gautier M, Allan R, et al. The nuclear hypoxia-regulated NLUCAT1 long non-coding RNA contributes to an aggressive phenotype in lung adenocarcinoma through regulation of oxidative stress [J]. Oncogene, 2019, 38(46): 7146-7165.
18
Huang H, Zhang W, Pan Y, et al. YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63-GPX2 Axis and ROS Accumulation [J]. Cancer Res, 2017, 77(21): 5769-5781.
19
王晓飞，赵辉，张国勇, 等. 基于数据挖掘分析ERO1L在肺腺癌中的表达及临床意义 [J]. 临床肺科杂志, 2018, 23(12): 2229-2233.
20
Potter M, Newport E, Morten KJ. The Warburg effect: 80 years on [J]. Biochem Soc Trans, 2016, 44(5): 1499-1505.
21
Jiang L, Zhao L, Bi J, et al. Glycolysis gene expression profilings screen for prognostic risk signature of hepatocellular carcinoma [J]. Aging (Albany NY), 2019, 11(23): 10861-10882.
22
Chen Z, Shi T, Zhang L, et al. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade [J]. Cancer Lett, 2016, 370(1): 153-164.
23
Minami K, Kamijo Y, Nishizawa Y, et al. Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine [J]. Anticancer Res, 2014, 34(9): 4767-4773.
24
Nobili S, Lapucci A, Landini I, et al. Role of ATP-binding cassette transporters in cancer initiation and progression [J]. Semin Cancer Biol, 2020, 60: 72-95.
25
Boswell-Casteel RC, Fukuda Y, Schuetz JD. ABCB6, an ABC Transporter Impacting Drug Response and Disease [J]. AAPS J, 2017, 20(1): 8.
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