Analytical and Bioanalytical Chemistry

, Volume 411, Issue 24, pp 6319–6328 | Cite as

Unraveling altered RNA metabolism in pancreatic cancer cells by liquid-chromatography coupling to ion mobility mass spectrometry

  • Simon Lagies
  • Manuel Schlimpert
  • Lukas M. Braun
  • Michel Kather
  • Johannes Plagge
  • Thalia Erbes
  • Uwe A. Wittel
  • Bernd KammererEmail author
Research Paper
Part of the following topical collections:
  1. Close-Up of Current Developments in Ion Mobility Spectrometry


Ion mobility coupling to mass spectrometry facilitates enhanced identification certitude. Further coupling to liquid chromatography results in multi-dimensional analytical methods, especially suitable for complex matrices with structurally similar compounds. Modified nucleosides represent a large group of very similar members linked to aberrant proliferation. Besides basal production under physiological conditions, they are increasingly excreted by transformed cells and subsequently discussed as putative biomarkers for various cancer types. Here, we report a method for modified nucleosides covering 37 species. We determined collisional cross-sections with high reproducibility from pure analytical standards. For sample purification, we applied an optimized phenylboronic acid solid-phase extraction on media obtained from four different pancreatic cancer cell lines. Our analysis could discriminate different subtypes of pancreatic cancer cell lines. Importantly, they could clearly be separated from a pancreatic control cell line as well as blank medium. m1A, m27G, and Asm were the most important features discriminating cancer cell lines derived from well-differentiated and poorly differentiated cancers. Eventually, we suggest the analytical method reported here for future tumor-marker identification studies.

Graphical abstract


Modified nucleosides Ion mobility mass spectrometry TWIMS Pancreatic cancer Biomarker 



This work was supported by Project B01 of the collaborative research initiative (SFB 1140 - KIDGEM) to M.S. and B.K. by the German Research Foundation (DFG).

Author contribution

Simon Lagies, Manuel Schlimpert, Lukas M. Braun, Thalia Erbes, Uwe A. Wittel, and Bernd Kammerer designed the study. Simon Lagies, Manuel Schlimpert, Lukas M. Braun, and Michel Kather performed the experiments and data analysis. Johannes Plagge aided in data processing and image creation. Simon Lagies, Lukas M. Braun, and Manuel Schlimpert wrote the manuscript.

Compliance with ethical standards

Informed consent

Informed consent was obtained for KHM1106 cell line usage and approved by the local Ethics Committee Freiburg (126/17 and 371/14) and registered at the German Clinical Trials Register (DRKS-ID DRKS00007561).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1814_MOESM1_ESM.pdf (3 mb)
ESM 1 (PDF 3044 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Simon Lagies
    • 1
    • 2
    • 3
  • Manuel Schlimpert
    • 1
    • 2
    • 3
  • Lukas M. Braun
    • 1
    • 4
  • Michel Kather
    • 1
    • 5
    • 6
  • Johannes Plagge
    • 1
  • Thalia Erbes
    • 7
  • Uwe A. Wittel
    • 4
  • Bernd Kammerer
    • 1
    • 8
    Email author
  1. 1.Center for Biological Systems Analysis ZBSAAlbert-Ludwigs-University FreiburgFreiburgGermany
  2. 2.Institute of Biology IIAlbert-Ludwigs-University FreiburgFreiburgGermany
  3. 3.Spemann Graduate School of Biology and MedicineAlbert-Ludwigs-University FreiburgFreiburgGermany
  4. 4.Department of General- and Visceral SurgeryUniversity of Freiburg Medical CenterFreiburgGermany
  5. 5.Faculty of Chemistry and PharmacyAlbert-Ludwigs-University FreiburgFreiburgGermany
  6. 6.Hermann Staudinger Graduate SchoolUniversity of FreiburgFreiburgGermany
  7. 7.Department of Gynecology and Obstetrics, Faculty of Medicine and Medical CenterUniversity of FreiburgFreiburgGermany
  8. 8.BIOSS Centre for Biological Signalling StudiesUniversity of FreiburgFreiburgGermany

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