中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 2
Feb.  2022
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(2): 409-414

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

DOI: 10.3969/j.issn.1001-5256.2022.02.028

  • Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China

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
  • Corresponding author: QU Linlin, taxue9455@sina.com
  • Received Date: 2021-07-07
  • Accepted Date: 2021-08-26
  • Published Date: 2022-02-20
    Abstract
  •   Objective  To investigate the gene mutations of Chinese patients with pancreatic cancer in the coastal regions of Eastern China, and to provide a basis for individualized treatment.  Methods  A total of 40 patients who were admitted and diagnosed with malignant pancreatic tumor after surgical treatment in The Affiliated Hospital of Qingdao University, Qingdao Municipal Hospital, Yantaishan Hospital, and Yantai Sino-France Friendship Hospital from January 2017 to June 2019 were enrolled. Next-generation sequencing (NGS) was used to detect gene mutations in tumor tissue and somatic cells, and the map of gene mutations was plotted to analyze genomic alterations. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups.  Results  Among the 40 patients, 34 (85.0%) had pancreatic ductal adenocarcinoma, 3 (7.5%) had solid pseudopapillary neoplasm of the pancreas, 1 (2.5%) had pancreatic neuroendocrine tumor, and 2 (5.0%) had unclear typing. KRAS (80.0%, 32/40), TP53 (70.0%, 28/40), CDKN2A (32.5%, 13/40), SMAD4 (17.5%, 7/40), and AKT2 (17.5%, 7/40) were the most common mutations, and there was no significant difference in survival time between the patients with these five common gene mutations (all P > 0.05).  Conclusion  NGS technology can provide comprehensive and accurate information of genomic alterations and may provide novel potential biomarkers for the diagnosis and precise treatment of pancreatic cancer. The analysis of mutant genes also lays a foundation for the individualized treatment of pancreatic cancer.

     

    • FullText(HTML)
  • loading
    • References(28)
  • [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.
    • Relative Articles
    • Supplements(1)
  • 王晶-华东沿海地区多中心40例胰腺肿瘤患者基因组图谱分析-附录1.pdf
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (373) PDF downloads(32) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return