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华东沿海地区多中心40例胰腺肿瘤患者基因组图谱分析

王晶 谭斌 赵志杰 仲灏辰 曲林林

引用本文:
Citation:

华东沿海地区多中心40例胰腺肿瘤患者基因组图谱分析

DOI: 10.3969/j.issn.1001-5256.2022.02.028
基金项目: 

山东省中青年科学家科研奖励基金 (BS2011YY004)

湖北省陈孝平科技发展基金 (CXPJJH12000002-2020057)

中华国际医学交流基金会2019年度黎介寿肠道屏障研究基金 (Z-2017-24-2009)

利益冲突声明:本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明:王晶、谭斌负责课题设计,资料分析,撰写论文;赵志杰、仲灏辰参与收集数据,修改论文;曲林林负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    曲林林,taxue9455@sina.com

Genomic profile of pancreatic tumor in the coastal regions of Eastern China: A multicenter analysis of 40 cases

Research funding: 

Scientific Research Award Fund for Young and Middle-Aged Scientists in Shandong Province (BS2011YY004);

Chen Xiaoping Science and Technology Development Fund of Hubei Province (CXPJJH12000002-2020057);

Li Jieshou Intestinal Barrier Research Foundation of China International Medical Exchange Foundation in 2019 (Z-2017-24-2009)

More Information
  • 摘要:   目的  探讨我国华东沿海地区胰腺癌患者的基因突变情况,为个体化治疗提供依据。  方法  选取2017年1月—2019年6月在青岛大学附属医院、青岛市立医院、烟台山医院、烟台中法友好医院收治并经手术治疗后诊断为胰腺恶性肿瘤的患者40例。采用下一代测序技术检测肿瘤组织和体细胞中的基因突变。绘制基因突变图谱,分析基因组改变。计数资料组间比较采用χ2检验或Fisher精确检验。采用Kaplan-Meier法绘制生存曲线,组间比较采用log-rank检验。  结果  40例患者中胰腺导管腺癌34例(85.0%),胰腺实性假乳头状肿瘤3例(7.5%),胰腺神经内分泌肿瘤1例(2.5%),分型不清2例(5.0%)。KRAS(80.0%,32/40)、TP53(70.0%,28/40)、CDKN2A(32.5%,13/40)、SMAD4(17.5%,7/40)和AKT2(17.5%,7/40)是最常见的突变。5种常见基因突变的生存时间差异均无统计学意义(P值均>0.05)。  结论  下一代测序技术能够提供全面、准确的基因组改变信息,可为胰腺癌的诊断和精确治疗提供新的潜在生物标志物。通过对突变基因进行分析,从而为胰腺癌的个体化治疗奠定基础。

     

  • 图  1  男女胰腺癌患者最常见的突变基因

    图  2  不同年龄组中最常见的突变基因

    图  3  神经和血管侵犯中最常见的突变基因

    图  4  胰腺癌突变基因生存分析

    注:a,KRAS基因突变生存分析;b,TP53基因突变生存分析;c,CDKN2A基因突变生存分析;d,AKT2基因突变生存分析;e,SMAD4基因突变生存分析;f,CTNNB1基因突变生存分析。

  • [1] SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1): 7-34. DOI: 10.3322/caac.21551.
    [2] STEUER CE, RAMALINGAM SS. Tumor mutation burden: Leading immunotherapy to the era of precision medicine?[J]. J Clin Oncol, 2018, 36(7): 631-632. DOI: 10.1200/JCO.2017.76.8770.
    [3] von HOFF DD, ERVIN T, ARENA FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine[J]. N Engl J Med, 2013, 369(18): 1691-1703. DOI: 10.1056/NEJMoa1304369.
    [4] CONROY T, PAILLOT B, FRANÇOIS E, et al. Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer—a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study[J]. J Clin Oncol, 2005, 23(6): 1228-1236. DOI: 10.1200/JCO.2005.06.050.
    [5] FRANCO J, WITKIEWICZ AK, KNUDSEN ES. CDK4/6 inhibitors have potent activity in combination with pathway selective therapeutic agents in models of pancreatic cancer[J]. Oncotarget, 2014, 5(15): 6512-6525. DOI: 10.18632/oncotarget.2270.
    [6] OSHIMA M, OKANO K, MURAKI S, et al. Immunohistochemically detected expression of 3 major genes (CDKN2A/p16, TP53, and SMAD4/DPC4) strongly predicts survival in patients with resectable pancreatic cancer[J]. Ann Surg, 2013, 258(2): 336-346. DOI: 10.1097/SLA.0b013e3182827a65.
    [7] BIANKIN AV, WADDELL N, KASSAHN KS, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes[J]. Nature, 2012, 491(7424): 399-405. DOI: 10.1038/nature11547.
    [8] KAWAGUCHI K, IGARASHI K, MIYAKE K, et al. MEK inhibitor trametinib in combination with gemcitabine regresses a patient-derived orthotopic xenograft (PDOX) pancreatic cancer nude mouse model[J]. Tissue Cell, 2018, 52: 124-128. DOI: 10.1016/j.tice.2018.05.003.
    [9] BOURNET B, BUSCAIL C, MUSCARI F, et al. Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities[J]. Eur J Cancer, 2016, 54: 75-83. DOI: 10.1016/j.ejca.2015.11.012.
    [10] MORTON JP, TIMPSON P, KARIM SA, et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer[J]. Proc Natl Acad Sci U S A, 2010, 107(1): 246-251. DOI: 10.1073/pnas.0908428107.
    [11] Cancer Genome Atlas Research Network. Integrated genomic characterization of pancreatic ductal adenocarcinoma[J]. Cancer Cell, 2017, 32(2): 185-203. DOI: 10.1016/j.ccell.2017.07.007.
    [12] WADDELL N, PAJIC M, PATCH AM, et al. Whole genomes redefine the mutational landscape of pancreatic cancer[J]. Nature, 2015, 518(7540): 495-501. DOI: 10.1038/nature14169.
    [13] ORMANNS S, HAAS M, REMOLD A, et al. The impact of SMAD4 loss on outcome in patients with advanced pancreatic cancer treated with systemic chemotherapy[J]. Int J Mol Sci, 2017, 18(5): 1094. DOI: 10.3390/ijms18051094.
    [14] XIA X, WU W, HUANG C, et al. SMAD4 and its role in pancreatic cancer[J]. Tumour Biol, 2015, 36(1): 111-119. DOI: 10.1007/s13277-014-2883-z.
    [15] CRANE CH, VARADHACHARY GR, YORDY JS, et al. Phase Ⅱ trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: Correlation of Smad4(Dpc4) immunostaining with pattern of disease progression[J]. J Clin Oncol, 2011, 29(22): 3037-3043. DOI: 10.1200/JCO.2010.33.8038.
    [16] OTTENHOF NA, MORSINK FH, TEN KATE F, et al. Multivariate analysis of immunohistochemical evaluation of protein expression in pancreatic ductal adenocarcinoma reveals prognostic significance for persistent Smad4 expression only[J]. Cell Oncol (Dordr), 2012, 35(2): 119-126. DOI: 10.1007/s13402-012-0072-x.
    [17] SHIN SH, KIM HJ, HWANG DW, et al. The DPC4/SMAD4 genetic status determines recurrence patterns and treatment outcomes in resected pancreatic ductal adenocarcinoma: A prospective cohort study[J]. Oncotarget, 2017, 8(11): 17945-17959. DOI: 10.18632/oncotarget.14901.
    [18] CHENG JQ, RUGGERI B, KLEIN WM, et al. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA[J]. Proc Natl Acad Sci U S A, 1996, 93(8): 3636-3641. DOI: 10.1073/pnas.93.8.3636.
    [19] RUGGERI BA, HUANG L, WOOD M, et al. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas[J]. Mol Carcinog, 1998, 21(2): 81-86.
    [20] CUI Y, WANG Q, WANG J, et al. Knockdown of AKT2 expression by RNA interference inhibits proliferation, enhances apoptosis, and increases chemosensitivity to the anticancer drug VM-26 in U87 glioma cells[J]. Brain Res, 2012, 1469: 1-9. DOI: 10.1016/j.brainres.2012.06.043.
    [21] NITULESCU GM, MARGINA D, JUZENAS P, et al. Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review)[J]. Int J Oncol, 2016, 48(3): 869-885. DOI: 10.3892/ijo.2015.3306.
    [22] CHEN D, NIU M, JIAO X, et al. Inhibition of AKT2 enhances sensitivity to gemcitabine via regulating PUMA and NF-κB signaling pathway in human pancreatic ductal adenocarcinoma[J]. Int J Mol Sci, 2012, 13(1): 1186-1208. DOI: 10.3390/ijms13011186.
    [23] LIU Q, TURNER KM, ALFRED YUNG WK, et al. Role of AKT signaling in DNA repair and clinical response to cancer therapy[J]. Neuro Oncol, 2014, 16(10): 1313-1323. DOI: 10.1093/neuonc/nou058.
    [24] KORINEK V, BARKER N, MORIN PJ, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma[J]. Science, 1997, 275(5307): 1784-1787. DOI: 10.1126/science.275.5307.1784.
    [25] LOGAN CY, NUSSE R. The Wnt signaling pathway in development and disease[J]. Annu Rev Cell Dev Biol, 2004, 20: 781-810. DOI: 10.1146/annurev.cellbio.20.010403.113126.
    [26] CLEVERS H. Wnt/beta-catenin signaling in development and disease[J]. Cell, 2006, 127(3): 469-480. DOI: 10.1016/j.cell.2006.10.018.
    [27] SINGHI AD, GEORGE B, GREENBOWE JR, et al. Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers[J]. Gastroenterology, 2019, 156(8): 2242-2253. DOI: 10.1053/j.gastro.2019.02.037.
    [28] WEISS GJ, BLAYDORN L, BECK J, et al. Phase Ib/Ⅱ study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma[J]. Invest New Drugs, 2018, 36(1): 96-102. DOI: 10.1007/s10637-017-0525-1.
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  • 收稿日期:  2021-07-07
  • 录用日期:  2021-08-26
  • 出版日期:  2022-02-20
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