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New Generation Sequencing in Cholangiocarcinoma and Gallbladder Cancer: Clinical Implications for Immunotherapy

Received: 20 June 2021    Accepted: 8 July 2021    Published: 16 July 2021
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Abstract

Objective: To explore the common mutation gene and mutation rule of cholangiocarcinoma and gallbladder cancer, and to confirm the therapeutic effect of PD1 inhibitor through follow-up. Method: From 2017 to 2019, 42 patients with intrahepatic cholangiocarcinoma (ICCA), 49 patients with extrahepatic cholangiocarcinoma (ECCA) and 40 patients with GBC were followed up in Eastern Hepatobiliary Hospital for new generation sequencing (NGS). And we also followed up 25 cases of cholangiocarcinoma with PD1 inhibitor and observed the therapeutic effect. Result: The result show that TP53, KRAS, ARID1A, CDKN2A, SMAD4 and ERBB are the most common mutations in ICCA. TP53, KRAS, CDKN2A, ARID2, SMAD4 and ARID1A are the most common mutations in ECCA. TP53, ERBB,CDKN2A, ARID1A, CCNE1 are the most common mutations in GBC. 25 patients who used PD1 inhibitors had no complete remission, 6 patients had partial remission, 6 patients had no effect at all, and the disease progressed. The objective remission rate reached 24% and progression free survival was 5.2±4.8 months. Conclusion: TP53, ARID1A, CDKN2A are the most common mutations in CCA or GBC. We believe that through continuous clinical trials, we will find drugs to inhibit these mutations. PD-1 inhibitor can be used as a choice for patients with advanced stage of CCA or GBC, but not all of them have good therapeutic effect. It is suggested to combine other methods for treatment.

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 7, Issue 4)
DOI 10.11648/j.ijcems.20210704.14
Page(s) 91-97
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Cholangiocarcinoma, Gallbladder Cancer, New Generation Gene Sequencing, PD-1 Inhibitor

References
[1] Tan JC, Coburn NG, Baxter NN, et al. Surgical management of intrahepatic cholangiocarcinoma--a population-based study. Ann Surg Oncol. 2008 (15): 600–608.
[2] Khan SA, Davidson BR, Goldin RD, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma. Gut. 2012 (61): 1657–69.
[3] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015 (65): 87–108.
[4] Grugan KD, Vega ME, Wong GS, et al. A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion. Cancer Biol Ther. 2013, 14 (9): 853-9. PMID: 2379258.
[5] Wang W, Cheng B, Miao L, et al. Mutant p53-R273H gains new function in sustained activation of EGFR signaling via suppressing MIR-27a expression. Cell Death Dis. 2013, 4: 574. PMID: 23559009.
[6] Leroy B, Anderson M, Soussi T. TP53 mutations in human cancer: database reassessment and prospects for the next decade. Hum Mutat. 2014, 35 (6): 672-88. PMID: 24665023.
[7] Senzer N, Nemunaitis J, Nemunaitis D, et al. Phase I study of a systemically delivered p53 nanoparticle in advanced solid tumors. Mol Ther. 21 (5), 1096-103. (2013). PMID: 23609015.
[8] Necchi A, Lo Vullo S, Mariani L, et al. An open-label, single-arm, phase 2 study of the Aurora kinase A inhibitor alisertib in patients with advanced urothelial cancer. Invest New Drugs. 34 (2), 236-42. (2016). PMID: 26873642.
[9] Valtorta E, Misale S, Sartore-Bianchi A. KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. Int J Cancer. 2013, 133 (5): 1259-65. PMID: 23404247.
[10] Kato S1, Goodman A2, Walavalkar V3, et al. Hyperprogressors after Immunotherapy: Analysis of Genomic Alterations Associated with Accelerated Growth Rate. Clin Cancer Res. 2017, 23 (15): 4242-4250. PMID: 28351930.
[11] Chung WC, Wang J, Zhou Y, et al. KrasG12D upregulates Notch signaling to induce gallbladder tumorigenesis in mice. Oncoscience. 2017, 4 (9-10): 131-138. PMID: 29142904.
[12] Bendell JC, Javle M, Bekaii-Saab TS, et al. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Br J Cancer. 2017. PMID: 28152546.
[13] Robert, C, Long, G, Brady, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015. PMID: 25399552.
[14] Engelman JA, Chen L, Tan X. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med. 2018, 14 (12), 1351-56. PMID: 19029981.
[15] Bitler BG, Fatkhutdinov N, Zhang R. Potential therapeutic targets in ARID1A-mutated cancers. Expert Opin Ther Targets. 2015, 19 (11): 1419-22. PMID: 26125128.
[16] Chandler RL, Damrauer JS, Raab JR, et al. Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling. Nat Commun. 2015, 6: 6118. PMID: 2562562582.
[17] Watanabe R, Ui A, Kanno S, Ogiwara H, et al. SWI/SNF factors required for cellular resistance to DNA damage include ARID1A and ARID1B and show interdependent protein stability. Cancer Res. 2014, 74 (9): 2465-75. PMID: 24788099.
[18] Fang JZ, Li C, Liu XY, et al. Hepatocyte-Specific Arid1a Deficiency Initiates Mouse Steatohepatitis and Hepatocellular Carcinoma. PLoS One. 2015, 10(11): 1430-42. PMID: 26569409.
[19] Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta. 1998, 1378 (2): 115-119. PMID: 9823374.
[20] Andrew H. Girgis. Clear Cell Renal Cell Carcinoma With Biallelic Inactivation Of CDKN2A/B On 9p21 Have Distinct Gene Expression Signature And Are Associated With Poor Prognosis. BioRxiv 2017. PMID: AB000220.
[21] Roa I, de Toro G, Schalper K, et al. Over expression of the HER2/neu Gene: A New Therapeutic Possibility for Patients with Advanced Gallbladder Cancer. Gastrointest Cancer Res. 7 (2), 42-8. (2014). PMID: 24799970.
[22] Pignochino Y, Sarotto I, Peraldo-Neia C, et al. Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC Cancer. 10, 631. (2010). PMID: 21087480.
[23] Gibbons GS1, Owens SR, Fearon ER, Nikolovska-Coleska Z. Regulation of Wnt signaling target gene expression by the histone methyltransferase DOT1L. ACS Chem Biol. 2015, 10(1): 109-114. DOI: 10.1021/cb500668u.
[24] Launonis B, Terblanche J, Lakehal M, et al. proximal bile duct cancer: high respectabiliy rate and 5 year survival. Ann Surg, 1999, 230 (2): 266.
[25] Burrell RA, McGranahan N, Bartek J, Swanton C. The causes and consequences of genetic heterogeneity in cancer evolution. Nature. 2013; 501: 338–345.
[26] Ozenne, P., Eymin, B., Brambilla, E. et al. The ARF tumor suppressor: structure, functions and status in cancer. Int J Cancer. 2010. DOI: 10.1002/ijc.25511.
[27] Dai Z, Xie J, Lei P. Knockdown of PREX2a inhibits the malignant phenotype of osteosarcoma cells. Mol Med Rep. 2016, 13: 1930-1936.
Cite This Article
  • APA Style

    Hao Song, Hongyan Ma, Yao Huang, Bin Yi, Xiaoqing Jiang. (2021). New Generation Sequencing in Cholangiocarcinoma and Gallbladder Cancer: Clinical Implications for Immunotherapy. International Journal of Clinical and Experimental Medical Sciences, 7(4), 91-97. https://doi.org/10.11648/j.ijcems.20210704.14

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    ACS Style

    Hao Song; Hongyan Ma; Yao Huang; Bin Yi; Xiaoqing Jiang. New Generation Sequencing in Cholangiocarcinoma and Gallbladder Cancer: Clinical Implications for Immunotherapy. Int. J. Clin. Exp. Med. Sci. 2021, 7(4), 91-97. doi: 10.11648/j.ijcems.20210704.14

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    AMA Style

    Hao Song, Hongyan Ma, Yao Huang, Bin Yi, Xiaoqing Jiang. New Generation Sequencing in Cholangiocarcinoma and Gallbladder Cancer: Clinical Implications for Immunotherapy. Int J Clin Exp Med Sci. 2021;7(4):91-97. doi: 10.11648/j.ijcems.20210704.14

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  • @article{10.11648/j.ijcems.20210704.14,
      author = {Hao Song and Hongyan Ma and Yao Huang and Bin Yi and Xiaoqing Jiang},
      title = {New Generation Sequencing in Cholangiocarcinoma and Gallbladder Cancer: Clinical Implications for Immunotherapy},
      journal = {International Journal of Clinical and Experimental Medical Sciences},
      volume = {7},
      number = {4},
      pages = {91-97},
      doi = {10.11648/j.ijcems.20210704.14},
      url = {https://doi.org/10.11648/j.ijcems.20210704.14},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20210704.14},
      abstract = {Objective: To explore the common mutation gene and mutation rule of cholangiocarcinoma and gallbladder cancer, and to confirm the therapeutic effect of PD1 inhibitor through follow-up. Method: From 2017 to 2019, 42 patients with intrahepatic cholangiocarcinoma (ICCA), 49 patients with extrahepatic cholangiocarcinoma (ECCA) and 40 patients with GBC were followed up in Eastern Hepatobiliary Hospital for new generation sequencing (NGS). And we also followed up 25 cases of cholangiocarcinoma with PD1 inhibitor and observed the therapeutic effect. Result: The result show that TP53, KRAS, ARID1A, CDKN2A, SMAD4 and ERBB are the most common mutations in ICCA. TP53, KRAS, CDKN2A, ARID2, SMAD4 and ARID1A are the most common mutations in ECCA. TP53, ERBB,CDKN2A, ARID1A, CCNE1 are the most common mutations in GBC. 25 patients who used PD1 inhibitors had no complete remission, 6 patients had partial remission, 6 patients had no effect at all, and the disease progressed. The objective remission rate reached 24% and progression free survival was 5.2±4.8 months. Conclusion: TP53, ARID1A, CDKN2A are the most common mutations in CCA or GBC. We believe that through continuous clinical trials, we will find drugs to inhibit these mutations. PD-1 inhibitor can be used as a choice for patients with advanced stage of CCA or GBC, but not all of them have good therapeutic effect. It is suggested to combine other methods for treatment.},
     year = {2021}
    }
    

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  • TY  - JOUR
    T1  - New Generation Sequencing in Cholangiocarcinoma and Gallbladder Cancer: Clinical Implications for Immunotherapy
    AU  - Hao Song
    AU  - Hongyan Ma
    AU  - Yao Huang
    AU  - Bin Yi
    AU  - Xiaoqing Jiang
    Y1  - 2021/07/16
    PY  - 2021
    N1  - https://doi.org/10.11648/j.ijcems.20210704.14
    DO  - 10.11648/j.ijcems.20210704.14
    T2  - International Journal of Clinical and Experimental Medical Sciences
    JF  - International Journal of Clinical and Experimental Medical Sciences
    JO  - International Journal of Clinical and Experimental Medical Sciences
    SP  - 91
    EP  - 97
    PB  - Science Publishing Group
    SN  - 2469-8032
    UR  - https://doi.org/10.11648/j.ijcems.20210704.14
    AB  - Objective: To explore the common mutation gene and mutation rule of cholangiocarcinoma and gallbladder cancer, and to confirm the therapeutic effect of PD1 inhibitor through follow-up. Method: From 2017 to 2019, 42 patients with intrahepatic cholangiocarcinoma (ICCA), 49 patients with extrahepatic cholangiocarcinoma (ECCA) and 40 patients with GBC were followed up in Eastern Hepatobiliary Hospital for new generation sequencing (NGS). And we also followed up 25 cases of cholangiocarcinoma with PD1 inhibitor and observed the therapeutic effect. Result: The result show that TP53, KRAS, ARID1A, CDKN2A, SMAD4 and ERBB are the most common mutations in ICCA. TP53, KRAS, CDKN2A, ARID2, SMAD4 and ARID1A are the most common mutations in ECCA. TP53, ERBB,CDKN2A, ARID1A, CCNE1 are the most common mutations in GBC. 25 patients who used PD1 inhibitors had no complete remission, 6 patients had partial remission, 6 patients had no effect at all, and the disease progressed. The objective remission rate reached 24% and progression free survival was 5.2±4.8 months. Conclusion: TP53, ARID1A, CDKN2A are the most common mutations in CCA or GBC. We believe that through continuous clinical trials, we will find drugs to inhibit these mutations. PD-1 inhibitor can be used as a choice for patients with advanced stage of CCA or GBC, but not all of them have good therapeutic effect. It is suggested to combine other methods for treatment.
    VL  - 7
    IS  - 4
    ER  - 

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Author Information
  • Department of Organ Transplantation, Eastern Hepatobiliary Surgery Hospital Affiliated to Shanghai Second Military Medical University, Shanghai, China

  • Pharmacy Department, Shenzhen Longhua District Central Hospital, Shenzhen, China

  • Department of Organ Transplantation, Eastern Hepatobiliary Surgery Hospital Affiliated to Shanghai Second Military Medical University, Shanghai, China

  • Department of Organ Transplantation, Eastern Hepatobiliary Surgery Hospital Affiliated to Shanghai Second Military Medical University, Shanghai, China

  • Department of Organ Transplantation, Eastern Hepatobiliary Surgery Hospital Affiliated to Shanghai Second Military Medical University, Shanghai, China

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