Skip to main content
SpringerLink
Log in

Blood-Based Circulating RNAs as Preventive, Diagnostic, Prognostic and Druggable Biomarkers for Pancreatic Ductal Adenocarcinoma

  • Chapter
  • First Online:
Translational Pancreatic Cancer Research

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with a poor prognosis. So far, serum CA19–9 (carbohydrate antigen 19–9) is the only blood biomarker that is routinely used in clinical practice. Recent studies have uncovered a stable presence of circulating RNAs in blood, which are studied and developed into preventive/predictive, diagnostic, prognostic and druggable biomarkers for PDAC. Blood RNAs consist of two major categories: mRNAs (messenger RNAs) and ncRNAs (noncoding RNAs); both of them exist either in a cell-free or in a cellular form. Due to the abundance of RNases in blood, cell-free mRNA poses only a limited clinical significance. Taking advantage of next-generation sequencing techniques, mRNA profiles of CTCs (circulating tumour cells) or TEPs (tumour-educated platelets) were shown to be promising diagnostic biomarkers for PDAC. As for ncRNAs, blood miRNA (microRNA) is presently the most characterized one. The alteration in blood miRNAs tends to take place late in the disease course of PDAC, arguing against its role as a preventive or predictive biomarker for early detection. Despite a lower specificity, blood miRNAs as diagnostic biomarkers are generally as useful as serum CA19–9. However, their measurement is still not as easy and standardized as serum CA19–9, which prevents their use in daily clinical practice. Meanwhile, many diagnostic blood miRNAs are also prognostic biomarkers that can be used for patient stratification. Finally, a few blood miRNAs are currently explored as druggable biomarkers at the preclinical stage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Salman B, Zhou D, Jaffee EM, Edil BH, Zheng LJO. Vaccine therapy for pancreatic cancer. Oncoimmunology. 2013;2:e26662.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27:1806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Okajima W, Komatsu S, Ichikawa D, et al. Liquid biopsy in patients with hepatocellular carcinoma: circulating tumor cells and cell-free nucleic acids. World J Gastroenterol. 2017;23:5650.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kishikawa T, Otsuka M, Ohno M, Yoshikawa T, Takata A, Koike K. Circulating RNAs as new biomarkers for detecting pancreatic cancer. World J Gastroenterol. 2015;21:8527.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kang CY, Wang J, Axell-House D, et al. Clinical significance of serum COL6A3 in pancreatic ductal adenocarcinoma. J Gastrointest Surg. 2014;18:7–15.

    Article  PubMed  Google Scholar 

  6. Funaki NO, Tanaka J, Kasamatsu T, et al. Identification of carcinoembryonic antigen mRNA in circulating peripheral blood of pancreatic carcinoma and gastric carcinoma patients. Life Sci. 1996;59:2187–99.

    Article  CAS  PubMed  Google Scholar 

  7. Funaki NO, Tanaka J, Hosotani R, Kogire M, Suwa H, Imamura M. Quantitative analysis of carcinoembryonic antigen messenger RNA in peripheral venous blood and portal blood of patients with pancreatic ductal adenocarcinoma. Clin Cancer Res. 1998;4:855–60.

    CAS  PubMed  Google Scholar 

  8. Mataki Y, Takao S, Maemura K, et al. Carcinoembryonic antigen messenger RNA expression using nested reverse transcription-PCR in the peripheral blood during follow-up period of patients who underwent curative surgery for biliary-pancreatic cancer: longitudinal analyses. Clin Cancer Res. 2004;10:3807–14.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang Y-L, Feng J-G, Gou J-M, Zhou L-X, Wang P. Detection of CK20mRNA in peripheral blood of pancreatic cancer and its clinical significance. World J Gastroenterol. 2005;11:1023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ishizone S, Yamauchi K, Kawa S, et al. Clinical utility of quantitative RT-PCR targeted to α1, 4-N-acetylglucosaminyltransferase mRNA for detection of pancreatic cancer. Cancer Sci. 2006;97:119–26.

    Article  CAS  PubMed  Google Scholar 

  11. Best MG, Sol N, Kooi I, et al. RNA-Seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics. Cancer Cell. 2015;28:666–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nature IHGSCJ. Initial sequencing and analysis of the human genome. Nature 2001;409:860.

    Google Scholar 

  13. Szymanski M, Barciszewska MZ, Erdmann VA, Barciszewski J. A new frontier for molecular medicine: noncoding RNAs. Biochim Biophys Acta. 1756;2005:65–75.

    Google Scholar 

  14. Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA–target recognition. PLoS Biol. 2005;3:e85.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem. 2010;285(23):17442–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A. 2011;108:5003–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bosetti C, Rosato V, Li D, et al. Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol. 2014;25:2065–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sharma A, Smyrk TC, Levy MJ, Topazian MA, Chari ST. Fasting blood glucose levels provide estimate of duration and progression of pancreatic cancer before diagnosis. Gastroenterology. 2018. 155(2):490–500.e2.

    Google Scholar 

  20. Mayers JR, Wu C, Clish CB, et al. Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development. Nat Med. 2014;20:1193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Duell EJ, Lujan-Barroso L, Sala N, et al. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. Int J Cancer. 2017;141:905–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Franklin O, Jonsson P, Billing O, et al. Plasma micro-RNA alterations appear late in pancreatic cancer. Ann Surg. 2018;267:775.

    Article  PubMed  Google Scholar 

  23. Ballehaninna UK, Chamberlain RS. Serum CA 19–9 as a biomarker for pancreatic cancer—a comprehensive review. Indian J Surg Oncol. 2011;2:88–100.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wang J, Chen J, Chang P, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila). 2009;2(9):807–13. CAPR-09-0094.

    Google Scholar 

  25. Ang L, Jun Y, Haeryoung K, et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res. 2013;19:3600–10.

    Article  Google Scholar 

  26. Tavano F, Gioffreda D, Valvano MR, et al. Droplet digital PCR quantification of miR-1290 as a circulating biomarker for pancreatic cancer. Scientific Reports 06 November 2018.

    Google Scholar 

  27. Ganepola Ap G, Rutledge JR, Paritosh S, Anusak Y, Chang DH. Novel blood-based microRNA biomarker panel for early diagnosis of pancreatic cancer. World J Gastrointest Oncol. 2014;6:22.

    Article  Google Scholar 

  28. Schultz NA, Christian D, Jensen BV, et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA. 2014;311:392.

    Article  CAS  PubMed  Google Scholar 

  29. Liu J, Gao J, Du Y, et al. Combination of plasma microRNAs with serum CA19–9 for early detection of pancreatic cancer. Int J Cancer. 2012;131:683–91.

    Article  CAS  PubMed  Google Scholar 

  30. Makoto A, Misa Y, Rie S, et al. Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int J Oncol. 2015;46:539–47.

    Article  Google Scholar 

  31. Alexander B, Stefanie NPD, Maike A, et al. Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma. Int J Cancer. 2013;132:E48–57.

    Article  Google Scholar 

  32. Li L, Zhang GQ, Chen H, et al. Plasma and tumor levels of Linc-pint are diagnostic and prognostic biomarkers for pancreatic cancer. Oncotarget. 2016;7:71773–81.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Xu HX, Liu L, Xiang JF, et al. Postoperative serum CEA and CA125 levels are supplementary to perioperative CA19–9 levels in predicting operative outcomes of pancreatic ductal adenocarcinoma. Surgery. 2017;161:373–84.

    Article  PubMed  Google Scholar 

  34. Dong Q, Yang XH, Zhang Y, et al. Elevated serum CA19–9 level is a promising predictor for poor prognosis in patients with resectable pancreatic ductal adenocarcinoma: a pilot study. World J Surg Oncol. 2014;12:1–8.

    Article  Google Scholar 

  35. Mahito M, Shuhei K, Daisuke I, et al. Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer. Br J Cancer. 2015;113:1467–76.

    Article  Google Scholar 

  36. Imamura T, Komatsu S, Ichikawa D, et al. Depleted tumor suppressor miR-107 in plasma relates to tumor progression and is a novel therapeutic target in pancreatic cancer. Sci Rep. 2017;7:e120.

    Article  Google Scholar 

  37. Kawaguchi T, Komatsu S, Ichikawa D, et al. Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer. Br J Cancer. 2013;108:361–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gebert LFR, Rebhan MAE, Crivelli SEM, Rémy D, Markus S, Jonathan H. Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Res. 2014;42:609–21.

    Article  CAS  PubMed  Google Scholar 

  39. Lanford RE, Hildebrandt-Eriksen ES, Andreas P, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science. 2010;327(5962):198–201.

    Article  CAS  PubMed  Google Scholar 

  40. Lai X, Wang M, Mcelyea SD, Sherman S, House M, Korc M. A microRNA signature in circulating exosomes is superior to exosomal glypican-1 levels for diagnosing pancreatic cancer. Cancer Lett. 2017;393:86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich (TUM), Munich, Germany

    Bo Kong & Helmut Friess

  2. Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China

    Bo Kong

Authors
  1. Bo Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helmut Friess
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Christoph W. Michalski

  2. Department of Internal Medicine I, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Jonas Rosendahl

  3. Department of Internal Medicine I, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Patrick Michl

  4. Department of Visceral, Vascular and Endocrine Surgery, University Hospital Halle (Saale), Halle (Saale), Sachsen-Anhalt, Germany

    Jörg Kleeff

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kong, B., Friess, H. (2020). Blood-Based Circulating RNAs as Preventive, Diagnostic, Prognostic and Druggable Biomarkers for Pancreatic Ductal Adenocarcinoma. In: Michalski, C., Rosendahl, J., Michl, P., Kleeff, J. (eds) Translational Pancreatic Cancer Research. Molecular and Translational Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-49476-6_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-49476-6_6

  • Published:

  • Publisher Name: Humana, Cham

  • Print ISBN: 978-3-030-49475-9

  • Online ISBN: 978-3-030-49476-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation