胃间质瘤患者辅助治疗前CDK4和TP53突变水平与预后的相关性

张帅, 申昌军. 胃间质瘤患者辅助治疗前CDK4和TP53突变水平与预后的相关性[J]. 中国中西医结合消化杂志, 2020, 28(9): 700-704. doi: 10.3969/j.issn.1671-038X.2020.09.11
引用本文: 张帅, 申昌军. 胃间质瘤患者辅助治疗前CDK4和TP53突变水平与预后的相关性[J]. 中国中西医结合消化杂志, 2020, 28(9): 700-704. doi: 10.3969/j.issn.1671-038X.2020.09.11
ZHANG Shuai, SHEN Chang-jun. Correlation between CDK4 and TP53 gene mutations and prognosis in patients with gastric stromal tumors before adjuvant therapy[J]. Chin J Integr Tradit West Med Dig, 2020, 28(9): 700-704. doi: 10.3969/j.issn.1671-038X.2020.09.11
Citation: ZHANG Shuai, SHEN Chang-jun. Correlation between CDK4 and TP53 gene mutations and prognosis in patients with gastric stromal tumors before adjuvant therapy[J]. Chin J Integr Tradit West Med Dig, 2020, 28(9): 700-704. doi: 10.3969/j.issn.1671-038X.2020.09.11

胃间质瘤患者辅助治疗前CDK4和TP53突变水平与预后的相关性

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    通讯作者: 申昌军,E-mail:zhang76shuau@163.com
  • 中图分类号: R735.2

Correlation between CDK4 and TP53 gene mutations and prognosis in patients with gastric stromal tumors before adjuvant therapy

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  • [目的]比较高复发转移风险与非高复发转移风险胃间质瘤(GST)患者TP53和CDK4基因的表达水平差异,TP53和CDK4基因的表达水平对高复发转移风险GST患者术后伊马替尼辅助治疗的预后影响。[方法]前瞻性纳入收治行根治切除术的143例原发性GST患者,根据《中国胃肠间质瘤诊断治疗专家共识》将原发性GST患者分为高风险组(62例)和非高风险组(81例)。术后取瘤组织做免疫组化检测,比较2组间p53(TP53基因编码的蛋白)和CDK4表达情况。高风险组给予术后伊马替尼辅助治疗,再根据免疫组化结果,将62例高风险组患者分为p53高表达组、p53低表达组和CDK4高表达组、CDK4低表达组进行亚组分析。分别比较高表达组和低表达组间5年无事件生存率。[结果]高风险组和低风险组的年龄和性别比例差异无统计学意义。而高风险组的原发肿瘤大小较非高风险组大,分别为(11.53±2.81)cm、(8.25±1.52)cm(P<0.001),且肿瘤的核分裂数较非高风险组多,分别为12.24±2.32、7.52±2.21(P<0.001)。免疫组化结果提示,高风险组p53蛋白表达水平较非高风险组高,而CDK4蛋白表达水平较非高风险组低。在高风险组中,p53高表达组的5年无事件生存率较低表达组低,分别为45.6%、78.4%(P=0.044);然而,CDK4高表达组的5年无事件生存率较低表达组高,分别为74.2%、48.4%(P=0.029)。[结论]高复发、高转移风险的GST患者TP53基因表达水平较高;CDK4表达水平较低。更高的TP53基因表达和更低的CDK4表达水平提示着高复发、转移风险的GST术后伊马替尼辅助治疗有更好的预后。
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  • [1]

    Luo XF,Zhou L H.Prognostic significance of neutrophil to lymphocyte ratio in patients with gastrointestinal stromal tumors:A meta-analysis[J].Clin Chim Acta,2017,477(1):7-12.

    [2]

    Gomes A,Bardales RF,Reis R,et al.Molecular analysis of c-Kit and PDGFRA in GISTs diagnosed by EUS[J].Am J Clin Pathol,2015,127(1):89-96.

    [3]

    Ahmad F,Lad P,Bhatia S,et al.Molecular spectrum of c-KIT and PDGFRA gene mutations in gastro intestinal stromal tumor:determination of frequency,distribution pattern and identification of novel mutations in Indian patients[J].Med Oncol,2015,32(1):1-11.

    [4]

    Wang Y,Fletcher JA.Cell cycle and dystrophin dysregulation in GIST[J].Cell Cycle,2015,14(17):2713-2714.

    [5]

    Neves LR,Oshima CT,Artigianineto R,et al.Ki67 and p53 in gastrointestinal stromal tumors-GIST[J].Arq Gastroenterol,2009,46(2):116-120.

    [6]

    Al-Bozom I A.p53 expression in gastrointestinal stromal tumors[J].Pathol Int,2010,51(7):519-523.

    [7]

    周东,毕瑞雪,杨勇 ,等.FAK在胃肠道间质瘤组织中的表达及其与诊断治疗关系的研究[J].医学信息,2016,29(26):226-228.

    [8]

    Kubota T.Gastrointestinal stromal tumor(GIST)and imatinib[J].Int J Clin Oncol,2006,11(3):184-189.

    [9]

    Van Glabbeke MM,Owzar K,Rankin C,et al.Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors(GIST):A meta-analyis based on 1,640 patients(pts)[J].J Clin Oncol,2010,28(7):1247-1253.

    [10]

    Joensuu H,Rutkowski P,Nishida T,et al.KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence[J].J Clin Oncol,2015,33(6):634-642.

    [11]

    Dematteo RP,Gold JS,Saran L,et al.Tumor mitotic rate,size,and location independently predict recurrence after resection of primary gastrointestinal stromal tumor(GIST)[J].Cancer,2010,112(3):608-615.

    [12]

    CSCO胃肠间质瘤专家委员会.中国胃肠间质瘤诊断治疗专家共识(2011年版)[J].临床肿瘤学杂志,2011,16(9):836-844.

    [13]

    王志生,李晓辉,任飞,等.免疫组化染色的操作技巧和注意事项[J].中国实用医药,2014,9(15):240-240.

    [14]

    Clark BZ,Dabbs DJ,Cooper KL,et al.Impact of progesterone receptor semiquantitative immunohistochemical result on Oncotype DX recurrence score:a quality assurance study of 1074 cases[J].Appl Immunohistochem Mol Morphol,2013,21(4):287-291.

    [15]

    Zhu X,Yang S,Lin W,et al.Roles of Cell Cyle Regulators Cyclin D1,CDK4,and p53 in Knee Osteoarthritis[J].Genet Test Mol Biomarkers,2016,20(9):529-534.

    [16]

    Liao P,Zeng SX,Zhou X,et al.Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding[J].Mol Cell,2017,68(6):1134-1146.

    [17]

    Leroy B,Anderson M,Soussi T.TP53 Mutations in Human Cancer:Database Reassessment and Prospects for the Next Decade[J].Hum Mutat,2014,35(6):672-688.

    [18]

    Ohnstad HO,Castro R,Sun J,et al.Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma[J].Cancer,2013,119(5):1013-1022.

    [19]

    Muller PAJ,Trinidad AG,Timpson P,et al.Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion[J].Oncogene,2013,32(10):1252-1265.

    [20]

    Somasundaram K.Tumor suppressor p53:regulation and function[J].Front Biosci,2000,5(5):424-437.

    [21]

    Muller PAJ,Vousden KH.p53 mutations in cancer[J].Nat Cell Biol,2013,15(1):2-8.

    [22]

    Ihle MA,Huss S,Jeske W,et al.Expression of cell cycle regulators and frequency of TP53 mutations in high risk gastrointestinal stromal tumors prior to adjuvant imatinib treatment[J].Plos One,2018,13(2):e0193048.

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收稿日期:  2019-09-04

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