• صفحه اصلی
  • Molecular Pathology and Methylation Assessment in Pancreatic Cancer; New Approach in Diagnosis and Treatment

اشتراک گذاری

آدرس مقاله


کد مقاله : JCHR-2008-1168 (R1) بازدید : 159 صفحه: 115 - 124

10.22034/jchr.2021.1907688.1168

نوع مقاله: پژوهشی

Molecular Pathology and Methylation Assessment in Pancreatic Cancer; New Approach in Diagnosis and Treatment

محورهای موضوعی :

Shagahyegh Mousavi 1 (Department of Molecular Medicine, Faculty of Medical Sciences, Qazvin University of Medical Sciences, Qazvin, Iran)
Mehdi Sahmani 2 (Department of Clinical Biochemistry and Genetic, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran)
Mehdi Azad 3 (Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran)

تاریخ دریافت : 1399/06/03 تاریخ پذیرش : 1400/08/19 تاریخ انتشار : 1401/12/10

کلید واژه: pathology, biomarkers, DNA methylation, Molecular, Epigenomics, Pancreatic Neoplasms (meSH system),

چکیده مقاله :

Pancreatic cancer is one of the deadliest cancers in world. Patient survival is less than 5%. However, early diagnosis of this cancer is very essential. In this article, we studied molecular pathology, epigenetic change in pancreatic cancer, and discussed the effect of methylation in inception and development of pancreatic cancer. By studying and identifying the genes methylated in this cancer, we can utilize them as biomarkers to be used to diagnose this cancer in a timely manner. Pancreatic cancer is realized as a multistage process characterized by the accumulation of genetic alterations companioned by typical histological conversion in pancreatic ductal cells. DNA methylation is one of the key changes in epigenetics in DNA structure. DNA methylation pattern as biomarker has explicit applications in diagnosis of cancers. Extensive disturbances of DNA methylation have been observed in cancer, causing changes in regulation of gene expression, developing oncogenesis. Understanding both epigenetic changes and DNA mutations promises for improving the characterization of malignancy to predict prognosis and treatment response. By recognition and understanding of molecular pathways and gene changes in this cancer, numerous drugs have been tested for targeted treatment that will allow identifying whole methylation patterns to recognize biomarkers for prognosis and early diagnosis of this cancer in future. By identifying pathways and aberrant methylation, screening and diagnosis are more and more necessary at early stages.

چکیده انگلیسی:

منابع و مأخذ:


  1. Danaei M., Haghdoost A., Momeni M., 2019. An Epidemiological Review of Common Cancers in Iran; A Review Article. Iranian Journal of Blood and Cancer.11 (3), 77-84.
    2.
  2. Bindra B S., Kaur H., Portillo S., Emiloju O., de de Jesus K G., 2019. B-cell Prolymphocytic Leukemia: Case Report and Challenges on a Diagnostic and Therapeutic Forefront. Cureus.11 (9).
    3.
  3. Maire F., Cibot J-O., Compagne C., Hentic O., Hammel P., Muller N., Ponsot P., Levy P., Ruszniewski P., 2017. Epidemiology of pancreatic cancer in France: descriptive study from the French national hospital database. European Journal of Gastroenterology & Hepatology.29 (8), 904-908.
    4.
  4. Herreros-Villanueva M., Bujanda L., 2016. Non-invasive biomarkers in pancreatic cancer diagnosis: what we need versus what we have. Annals of translational medicine.4 (7).
    5.
  5. Ilic M., Ilic I., 2016. Epidemiology of pancreatic cancer. World journal of gastroenterology.22 (44), 9694.
    6.
  6. Mocci E., Klein A P., 2018. Epidemiology of pancreatic cancer. The pancreas: An integrated textbook of basic science, medicine, and surgery. 665-672.
    7.
  7. Goudarzi M., Heidary M., Azad M., Fazeli M., Goudarzi H.,2016. Evaluation of antimicrobial susceptibility and integron carriage in Helicobacter pylori isolates from patients. Gastroenterology and Hepatology from bed to Bench.9 (Suppl1), S47.
    8.
  8. Buscail L., 2017. Commentary: Pancreatic cancer: is the worst to come? International Journal of Epidemiology.46(6), 1774-1775.
    9.
  9. Swords D.S., Firpo M.A., Scaife C.L., Mulvihill S.J., 2016. Biomarkers in pancreatic adenocarcinoma: current perspectives. OncoTargets and therapy.9, 7459.
    10.
  10. Dehghanifard A., Kaviani S., Abroun S., Mehdizadeh M., Saiedi S., Maali A., Ghaffari S., Azad M., 2018.Various signaling pathways in multiple myeloma cells and effects of treatment on these pathways. Clinical Lymphoma Myeloma and Leukemia.18(5), 311-320.
    11.
  11. Kamisawa T., Wood L D., Itoi T., Takaori K., 2016.Pancreatic cancer. The Lancet. 388 (10039), 73-85.
    12.
  12. Feig C., Gopinathan A., Neesse A., Chan D S., Cook N., Tuveson D A., The pancreas cancer microenvironment. AACR: 2012.
    13.
  13. Sato N., Kohi S., Hirata K., Goggins M., 2013. Role of hyaluronan in pancreatic cancer biology and therapy: Once again in the spotlight. Cancer Science.107(5), 569-575.
    14.
  14. Singh D., Upadhyay G., Srivastava R., Shankar S., 2015. Review: Recent advances in pancreatic cancer: biology, treatment, and prevention. BBA-Reviews On Cancer, 185613.27.
    15.
  15. Natale F., Vivo M., Falco G., Angrisano T., 2019. Deciphering DNA methylation signatures of pancreatic cancer and pancreatitis. Clinical Epigenetics.11(1), 132.
    16.
  16. DiMagno M J., DiMagno E P., 2013. Chronic pancreatitis. Current opinion in gastroenterology.29 (5), 531.
    17.

17.Bournet B., Buscail C., Muscari F., Cordelier P., Buscail L., 2016. Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities. European Journal of Cancer. 54, 75-83.

  1. Li L., Choi J.Y., Lee K.M., Sung H., Park S.K., Oze I., Pan K.F., You W.C., Chen Y.X., Fang J.Y., 2012. DNA methylation in peripheral blood: a potential biomarker for cancer molecular epidemiology. Journal of Epidemiology.22 (5), 384-394.
    2.
  2. Chen M., Xue X., Wang F., An Y., Tang D., Xu Y., Wang H., Yuan Z., Gao W., Wei J., 2012. Expression and promoter methylation analysis of ATP-binding cassette genes in pancreatic cancer. Oncology reports.27 (1), 265-269.
    3.
  3. Lach R., Schön J., Krolopp T., Arndt S., Langer B., Grellmann W ., 2016. In Depth‐Sensing Macroindentation Test and Stepped Isothermal Method–Accelerated Assessment of the Local Retardation Behaviour of Thermoplastic Polymers, Macromolecular Symposia, Wiley Online Library. pp. 60-65.
    4.
  4. Rahmani T., Azad M., Chahardouli B., Nasiri H., Vatanmakanian M., Kaviani S., 2017. Patterns of DNMT1 promoter methylation in patients with acute lymphoblastic leukemia. International Journal of Hematology-oncology and Stem Cell Research.11(3), 172.
    5.
  5. Alipour S., Sakhinia E., Khabbazi A., Samadi N., Babaloo Z., Azad M., Abolhasani S., Farhadi J., Jadideslam G., Roshanravan N., 2020. Methylation status of interleukin-6 gene promoter in patients with behcet's disease. Reumatologia Clinica.. 16(3), 229-234.
    6.
  6. Ghaneh P., Costello E., Neoptolemos J.P., 2007. Biology and management of pancreatic cancer. Gut. 56(8), 1134-52.
    7.
  7. Delpu Y., Hanoun N., Lulka H., Sicard F., Selves J., Buscail L., Torrisani J., Cordelier P., 2011. Genetic and epigenetic alterations in pancreatic carcinogenesis. Curr Genomics.12(1), 15-24.
    8.
  8. Natale F., Vivo M., Falco G., Angrisano T., 2019. Deciphering DNA methylation signatures of pancreatic cancer and pancreatitis. Clinical Epigenetics.11(1), 132.
    9.
  9. Polireddy K., Chen Q., 2016. Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment. J Cancer.7(11), 1497-514.
    10.
  10. Neesse A., Michl P., Frese K K., Feig C., Cook N., Jacobetz M A., Lolkema M P., Buchholz M., Olive K P., Gress T M., Tuveson D A., 2011.Stromal biology and therapy in pancreatic cancer. Gut. 60 (6), 861-8.
    11.
  11. Saiki Y., Horii A., 2014.Molecular pathology of pancreatic cancer. Pathol Int.64 (1), 10-9.
    12.
  12. Hackeng W.M., Hruban R.H., Offerhaus G.J., Brosens L.A., 2016. Surgical and molecular pathology of pancreatic neoplasms. Diagn Pathol.11(1), 47.
    13.
  13. Liu J., Cui X., Jiang J., Cao D., He Y., Wang H., 2017. Uncoordinated expression of DNA methylation-related enzymes in human cancer. Epigenetics Chromatin.10(1), 61.
    14.
  14. Distler M., Aust D., Weitz J., Pilarsky C., Grützmann R., 2014. Precursor lesions for sporadic pancreatic cancer: PanIN, IPMN, and MCN. Biomed Res Int. 2014, 474905.
    15.
  15. Stark A., Eibl G., 2015. Pancreatic ductal adenocarcinoma. Pancreapedia: The Exocrine Pancreas Knowledge Base. Version 1.0, May 23, 2015 [DOI: 10.3998/panc.2015.14]
    16.
  16. Lewis M.A., Yao J.C., 2014. Molecular pathology and genetics of gastrointestinal neuroendocrine tumours. Current Opinion in Endocrinology, Diabetes and Obesity. 21(1), 22-27.
    17.
  17. Wolfgang C.L., Herman J.M., Laheru D.A., Klein A.P., Erdek M.A., Fishman E.K., Hruban R.H., 2013. Recent progress in pancreatic cancer. CA Cancer J Clin.63 (5), 318-48.
    18.
  18. Neesse A., Michl P., Frese K K., Feig C., Cook N., Jacobetz M.A., Lolkema M.P., Buchholz M., Olive K.P., Gress T.M., 2011. Stromal biology and therapy in pancreatic cancer. Gut. 60(6), 861-868.
    19.

36.Ying H., Dey P., Yao W., Kimmelman A.C., Draetta G.F., Maitra A., DePinho R.A., 2016. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 30(4), 355-85.

  1. Ram Makena M., Gatla H., Verlekar D., Sukhavasi S., pandey M.K., 2019. Wnt/β-Catenin Signaling: The Culprit in Pancreatic Carcinogenesis and Therapeutic Resistance. Int J Mol Sci. 20(17), 4242.
    2.
  2. Cowan R.W., Maitra A., 2014. Genetic progression of pancreatic cancer. Cancer J. 20(1), 80-4.
    3.
  3. Hu B., Shi C., Jiang H X., Qin S.Y., 2017. Identification of novel therapeutic target genes and pathway in pancreatic cancer by integrative analysis. Medicine (Baltimore). 96(42), e8261.
    4.
  4. Yuan Q.Y., Gu Y.P., Wang C.J., Zhang H., Wang X.P., 2015. Identification of dysregulated pathways associated with pancreatic cancer by survival analysis. Mol Med Rep.11(1), 277-82.
    5.
  5. Macgregor-Das A.M., Iacobuzio-Donahue C.A., 2013. Molecular pathways in pancreatic carcinogenesis. J Surg Oncol. 107(1), 8-14.
    6.
  6. Ahmed S., Bradshaw A.D., Gera S., Dewan M.Z., Xu R., 2017. The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance. J Clin Med. 6(1), 5
    7.
  7. Furukawa T., Sunamura M., Horii A., 2006. Molecular mechanisms of pancreatic carcinogenesis. Cancer Sci. 97(1), 1-7.
    8.
  8. Fernandez-Zapico M.E., Urrutia R., 2004. Molecular pathways of pancreatic carcinogenesis. Drug Discovery Today: Disease Mechanisms.1(2), 247-252.
    9.
  9. Ghorban K., Shanaki M., Mobarra N., Azad M., Asadi J., Pakzad R., Ehteram H., 2016. Apolipoproteins A1, B, and other prognostic biochemical cardiovascular risk factors in patients with beta-thalassemia major. Hematology. 21(2), 113-20.
    10.
  10. Makohon-Moore A., Iacobuzio-Donahue C.A., 2016. Pancreatic cancer biology and genetics from an evolutionary perspective. Nat Rev Cancer. 16(9), 553-65.
    11.
  11. Sun X.D., Liu X.E., Huang D.S., 2013. Curcumin reverses the epithelial-mesenchymal transition of pancreatic cancer cells by inhibiting the Hedgehog signaling pathway. Oncol Rep. 29(6), 2401-7.
    12.
  12. Kulis M., Esteller M., 2010. DNA methylation and cancer. Adv Genet.70, 27-56.
    13.
  13. Holm K., Hegardt C., Staaf J., Vallon-Christersson J., Jönsson G., Olsson H., Borg A., Ringnér M., 2010. Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns. Breast Cancer Res. 12(3), R36.
    14.
  14. Maali A., Atashi A., Ghaffari S., Kouchaki R., Abdolmaleki F., Azad M., 2018. A Review on Leukemia and iPSC Technology: Application in Novel Treatment and Future. Curr Stem Cell Res Ther. 13(8), 665-675.
    15.
  15. Baylin S.B., Jones P.A., 2016. Epigenetic Determinants of Cancer. Cold Spring Harb Perspect Biol. 8(9), a019505.
    16.

52.Manoochehri M., Bandehpour M., Kazemi B., 2013. A convenient method to generate methylated and un-methylated control DNA in methylation studies. Molecular Biology Research Communications. 2(3), 57-61.

  1. Jasek K., Kubatka P., Samec M., Liskova A., Smejkal K., Vybohova D., Bugos O., Biskupska-Bodova K., Bielik T., Zubor P., 2019. DNA methylation status in cancer disease: modulations by plant-derived natural compounds and dietary interventions. Biomolecules. 9(7), 289.
    2.
  2. Sandoval J., Esteller M., 2012. Cancer epigenomics: beyond genomics. Curr Opin Genet Dev. 22(1), 50-5.
    3.
  3. Dawson M.A., Kouzarides T., 2012. Cancer epigenetics: from mechanism to therapy. Cell.150(1), 12-27.
    4.

56.Zilberman D., Gehring M., Tran R.K., Ballinger T., Henikoff S., 2007. Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription. Nat Genet. 39(1), 61-9.

  1. Alipour S., Sakhinia E., Khabbazi A., Samadi N., Babaloo Z., Azad M., Abolhasani S., Farhadi J., Jadideslam G., Roshanravan N., Nouri M., 2020. Methylation status of interleukin-6 gene promoter in patients with Behçet's disease. Reumatol Clin (Engl Ed). 16(3), 229-234.
    2.
  2. Sharma S., Kelly T.K., Jones P.A., 2010. Epigenetics in cancer. Carcinogenesis.31(1), 27-36.
    3.
  3. Toraño E.G., Petrus S., Fernandez A.F., Fraga M.F., 2012. Global DNA hypomethylation in cancer: review of validated methods and clinical significance. Clin Chem Lab Med. 50(10), 1733-42.
    4.
  4. Liggett T., Melnikov A., Yi Q.L., Replogle C., Brand R., Kaul K., Talamonti M., Abrams R.A., Levenson V., 2010. Differential methylation of cell-free circulating DNA among patients with pancreatic cancer versus chronic pancreatitis. Cancer.116 (7), 1674-80.
    5.
  5. Hong S.M., Park J.Y., Hruban R.H., Goggins M., 2011. Molecular signatures of pancreatic cancer. Arch Pathol Lab Med. 135(6), 716-27.
    6.
  6. Peng D.F., Kanai Y., Sawada M., Ushijima S., Hiraoka N., Kitazawa S., Hirohashi S., 2006. DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT1) during multistage carcinogenesis of the pancreas. Carcinogenesis. 27(6), 1160-8.
    7.
  7. Azad M., Kaviani S., Soleymani M., Nourouzinia M., Hajfathali A., 2009. Common polymorphism’s analysis of thiopurine S-methyltransferase (TPMT) in Iranian population. Yakhteh Med J. 11, 311-316.
    8.

64.Abukiwan A., Berger M.R., 2018.  Epigenetics: Dissecting Gene Expression Alteration in PDAC. In Advances in DNA Repair, IntechOpen.

65.Tan A.C., Jimeno A., Lin S.H., Wheelhouse J., Chan F., Solomon A., Rajeshkumar N.V., Rubio-Viqueira B.,Hidalgo M., 2009. Characterizing DNA methylation patterns in pancreatic cancer genome. Mol Oncol. 3(5-6), 425-38.

66.Ueki T., Toyota M., Sohn T., Yeo C.J., Issa J.P., Hruban R.H., Goggins M., 2000. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res. 60(7), 1835-9.

67.Henriksen S.D., Madsen P.H., Larsen A.C., Johansen M.B., Drewes A.M., Pedersen I.S., Krarup H., Thorlacius-Ussing O., 2016. Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma. Clin Epigenetics. 8, 117.

68.Sato N., Fukushima N., Maitra A., Matsubayashi H.,Yeo C.J., Cameron J.L., Hruban R.H., Goggins M., 2003. Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res. 63(13), 3735-42.

69.Vincent A., Omura N., Hong S M., Jaffe A., Eshleman J., Goggins M., 2011. Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. Clin Cancer Res. 17 (13), 4341-54.

  1. Omura N., Goggins M., 2009. Epigenetics and epigenetic alterations in pancreatic cancer. Int J Clin Exp Pathol. 2(4), 310-26.
    2.

71.Sato N., Fukushima N., Chang R., Matsubayashi H., Goggins M., 2006. Differential and epigenetic gene expression profiling identifies frequent disruption of the RELN pathway in pancreatic cancers. Gastroenterology. 130 (2), 548-65.

72.Yi J.M., Guzzetta A.A., Bailey V.J., Downing S.R., Van Neste L., Chiappinelli K.B., Keeley B.P., Stark A., Herrera A., Wolfgang C., Pappou E.P., Iacobuzio-Donahue C.A., Goggins M.G., Herman J.G., Wang T.H., Baylin S.B., Ahuja N., 2013. Novel methylation biomarker panel for the early detection of pancreatic cancer. Clin Cancer Res.19(23), 6544-6555.

  1. Hao X., Luo H., Krawczyk M., Wei W., Wang W., Wang J., Flagg K., Hou J., Zhang H., Yi S., Jafari M., Lin D., Chung C., Caughey B A., Li G., Dhar D., Shi W., Zheng L., Hou R., Zhu J., Zhao L., Fu X., Zhang E., Zhang C., Zhu J K., Karin M., Xu R H., Zhang K., 2017. DNA methylation markers for diagnosis and prognosis of common cancers. Proc Natl Acad Sci U.S.A. 114(28), 7414-7419.
    2.

74.Henriksen S.D., Madsen P.H., Larsen A.C., Johansen M.B., Pedersen I.S., Krarup H., Thorlacius-Ussing O., 2017. Cell-free DNA promoter hypermethylation in plasma as a predictive marker for survival of patients with pancreatic adenocarcinoma. Oncotarget. 8(55), 93942-93956.

75.Kisiel J.B., Raimondo M., Taylor W.R., Yab T.C., Mahoney D.W., Sun Z., Middha S., Baheti S., Zou H., Smyrk T.C., Boardman L.., Petersen G.M., Ahlquist D.A., 2015. New DNA Methylation Markers for Pancreatic Cancer: Discovery, Tissue Validation, and Pilot Testing in Pancreatic Juice. Clin Cancer Res. 21(19), 4473-81.

سکوی نشر دانش

سند یا سکوی نشر دانش ،سامانه ای جهت مدیریت حوزه علمی و پژوهشی نشریات دانشگاه آزاد می باشد

پیوندهای سایت

مراکز مرتبط

پشتیبانی

صفحات رسمی

حقوق این وب‌سایت متعلق به سامانه مدیریت نشریات دانشگاه آزاد اسلامی است.
حق نشر © 1403-1400

صفحه اصلی| عضویت/ ورود| درباره سند| تماس با ما|
[English] [العربية] [en] [ar]