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中华肝脏外科手术学电子杂志 ›› 2023, Vol. 12 ›› Issue (04) : 449 -453. doi: 10.3877/cma.j.issn.2095-3232.2023.04.017

基础研究

蛋白磷酸酶1G在肝细胞癌中的表达及其与预后的关系
孙翀, 徐成臣, 王辉, 谢应海, 王琦()   
  1. 232001 安徽省淮南市,安徽理工大学第一附属医院肝胆胰脾外科
  • 收稿日期:2023-02-27 出版日期:2023-08-10
  • 通信作者: 王琦
  • 基金资助:
    2019年蚌埠医学院自然科学重点项目(BYKY2019323ZD)

Expression level of protein phosphatase 1G in hepatocellular carcinoma and its relationship with prognosis

Chong Sun, Chengchen Xu, Hui Wang, Yinghai Xie, Qi Wang()   

  1. Department of Hepatobiliary, Pancreatic and Splenic Surgery, the First Affiliated Hospital of Anhui University of Science and Technology, Huainan 232001, China
  • Received:2023-02-27 Published:2023-08-10
  • Corresponding author: Qi Wang
引用本文:

孙翀, 徐成臣, 王辉, 谢应海, 王琦. 蛋白磷酸酶1G在肝细胞癌中的表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2023, 12(04): 449-453.

Chong Sun, Chengchen Xu, Hui Wang, Yinghai Xie, Qi Wang. Expression level of protein phosphatase 1G in hepatocellular carcinoma and its relationship with prognosis[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2023, 12(04): 449-453.

目的

探讨蛋白磷酸酶1G(PPM1G)在肝细胞癌(肝癌)组织中的表达及其与患者预后的关系。

方法

采用Oncomine和癌症基因组图谱(TCGA)公共数据集分析PPM1G在肝癌及癌旁组织中的表达及其与患者预后的关系。10对肝癌及配对癌旁组织标本来源于2018年5月至2021年4月安徽理工大学第一附属医院手术切除的10例肝癌患者。患者均签署知情同意书,符合医学伦理学规定。其中男7例,女3例;年龄57~68岁,中位年龄64岁。采用荧光定量PCR法及免疫组化验证肝癌PPM1G表达及其与预后的关系。两组PPM1G表达比较采用t检验。生存分析采用Kaplan-Meier法和Log-rank检验。

结果

Oncomine数据库分析显示,PPM1G基因在肝癌中表达上调。TCGA数据库分析显示,肝癌组织PPM1G mRNA平均相对表达量为3.73±0.22,明显高于癌旁组织的3.45±0.11(t=2.99,P<0.05);肝癌PPM1G低表达组患者总体生存率明高于肝癌PPM1G高表达组患者(HR=1.76,P<0.05)。荧光定量PCR分析显示,肝癌组织PPM1G mRNA相对表达量为4.46±0.38,明显高于癌旁组织的2.86±0.33(t=1.32,P<0.05)。免疫组化法检测显示,肝癌组织PPM1G高表达组PPM1G蛋白相对表达量为23.0±4.0,明显高于PPM1G低表达组的5.0±1.0(t=3.78,P<0.05)。生存分析显示,PPM1G高、低表达组中位生存期分别为32、41个月,PPM1G高表达组患者的总体生存率明显低于PPM1G低表达组患者(χ2=0.673,P<0.05)。

结论

PPM1G在肝癌中高表达,PPM1G表达水平与肝癌患者的预后成负相关,其可能是肝癌预后评价的潜在指标。

Objective

To investigate the expression level of protein phosphatase 1G (PPM1G) in human hepatocellular carcinoma (HCC) and its relationship with the prognosis of HCC patients.

Methods

The expression level of PPM1G in HCC and adjacent tissues and its relationship with prognosis of HCC patients were analyzed by using Oncomine and The Cancer Genome Atlas (TCGA) databases. 10 pairs of HCC and matched adjacent tissues were collected from 10 HCC patients undergoing surgical resection in the First Affiliated Hospital of Anhui University of Science and Technology from May, 2018 to April, 2021. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 7 patients were male and 3 female, aged from 57 to 68 years, with a median age of 64 years. The expression level of PPM1G in HCC and its relationship with clinical prognosis were investigated by quantitative fluorescence PCR and immunohistochemical staining. The expression levels of PPM1G between two groups were compared byt test. Survival analysis was performed Kaplan-Meier method and Log-rank test.

Results

Oncomine database analysis showed that the expression level of PPM1G mRNA was up-regulated in HCC. TCGA database revealed that the average relative expression level of PPM1G mRNA was 3.73±0.22 in HCC, significantly higher than 3.45±0.11 in adjacent tissues (t=2.99, P<0.05). The overall survival rate of HCC patients with low PPM1G expression was significantly higher than that of those with high PPM1G expression (HR=1.76,P<0.05). Quantitative fluorescence PCR showed that, the relative expression level of PPM1G mRNA was 4.46±0.38 in HCC tissues, significantly higher than 2.86±0.33 in adjacent tissues (t=1.32, P<0.05). Immunohistochemical staining showed that, the relative expression level of the PPM1G protein was 23.0 ±4.0 with high PPM1G expression in HCC tissues, significantly higher than 5.0 ±1.0 with low PPM1G expression (t=3.78, P<0.05). Survival analysis showed that the median survival of patients with high and low PPM1G expression was 32 and 41 months. The overall survival rate of patients with high PPM1G expression was significantly lower than those with low PPM1G expression (χ2=0.673, P<0.05).

Conclusions

PPM1G is highly expressed in HCC. The expression level of PPM1G is negatively correlated with clinical prognosis of HCC patients, which may serve as a potential prognostic biomarker for HCC patients.

图1 PPM1G在肝癌中表达的研究报道汇总(Oncomine数据库)注:PPM1G为蛋白磷酸酶1G
表1 Oncomine数据库中不同肿瘤PPM1G的表达(项)
表2 肝癌PPM1G表达与患者临床病理学参数的关系(TCGA数据库)
图2 PPM1G的表达与肝癌患者预后的Kaplan-Meier生存曲线(TCGA数据库)注:PPM1G为蛋白磷酸酶1G,TCGA为癌症基因组图谱
图3 PPM1G的表达与肝癌患者预后的Kaplan-Meier生存曲线注:PPM1G为蛋白磷酸酶1G
[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016[J]. CA Cancer J Clin, 2016, 66(1):7-30.
[2]
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.
[3]
Chen WQ, Zheng RS, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[4]
中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版)[J]. 中华消化外科杂志, 2022, 21(2):143-168.
[5]
Malakar P, Shilo A, Mogilevsky A, et al. Long noncoding RNA MALAT1 promotes hepatocellular carcinoma development by SRSF1 upregulation and mTOR activation[J]. Cancer Res, 2017, 77(5):1155-1167.
[6]
Luo CL, Cheng YM, Liu YG, et al. SRSF2 regulates alternative splicing to drive hepatocellular carcinoma development[J]. Cancer Res, 2017, 77(5):1168-1178.
[7]
Yuan JH, Liu XN, Wang TT, et al. The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1[J]. Nat Cell Biol, 2017, 19(7):820-832.
[8]
Gudipaty SA, McNamara RP, Morton EL, et al. PPM1G binds 7SK RNA and hexim1 to block P-TEFb assembly into the 7SK snRNP and sustain transcription elongation[J]. Mol Cell Biol, 2015, 35(22): 3810-3828.
[9]
Yu K, Tian HB, Deng HY. PPM1G restricts innate immune signaling mediated by STING and MAVS and is hijacked by KSHV for immune evasion[J]. Sci Adv, 2020, 6(47):eabd0276.
[10]
Liu JY, Stevens PD, Eshleman NE, et al. Protein phosphatase PPM1G regulates protein translation and cell growth by dephosphorylating 4E binding protein 1 (4E-BP1)[J]. J Biol Chem, 2013, 288(32): 23225-23233.
[11]
Hanahan D. Hallmarks of cancer: new dimensions[J]. Cancer Discov, 2022, 12(1):31-46.
[12]
Mo ZM, Liu DY, Rong DD, et al. Hypoxic characteristic in the immunosuppressive microenvironment of hepatocellular carcinoma[J]. Front Immunol, 2021(12):611058.
[13]
Cramer T, Vaupel P. Severe hypoxia is a typical characteristic of human hepatocellular carcinoma: scientific fact or fallacy?[J].J Hepatol, 2022, 76(4):975-980.
[14]
Qin SK, Chen ZD, Liu Y, et al. A phaseⅡ study of anti-PD-1 antibody camrelizumab plus FOLFOX4 or GEMOX systemic chemotherapy as first-line therapy for advanced hepatocellular carcinoma or biliary tract cancer[J]. J Clin Oncol, 2019(37):4074.
[15]
Chen XF, Wu XF, Wu H, et al. Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phaseⅡ trial[J]. J Immunother Cancer, 2020, 8(2):e001240.
[16]
Yu WD, Sun G, Li J, et al. Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and/or chemotherapy[J]. Cancer Lett, 2019(452):66-70.
[17]
Limagne E, Thibaudin M, Nuttin L, et al. Trifluridine/tipiracil plus oxaliplatin improves PD-1 blockade in colorectal cancer by inducing immunogenic cell death and depleting macrophages[J]. Cancer Immunol Res, 2019, 7(12):1958-1969.
[18]
Qin SK, Bai YX, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia[J]. J Clin Oncol, 2013, 31(28):3501-3508.
[19]
Wu XM, Gu ZK, Chen Y, et al. Application of PD-1 blockade in cancer immunotherapy[J]. Comput Struct Biotechnol J, 2019(17):661-674.
[20]
Xu WQ, Liu K, Chen MJ, et al. Immunotherapy for hepatocellular carcinoma: recent advances and future perspectives[J]. Ther Adv Med Oncol, 2019(11):175883591986269.
[21]
Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies[J]. Nat Rev Drug Discov, 2019, 18(3):197-218.
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