Native Glycan Fragments Detected by MALDI-FT-ICR Mass Spectrometry Imaging Impact Gastric Cancer Biology and Patient Outcome

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Oct 6

PMID 28978092

Citations 19

Authors

Thomas Kunzke

Benjamin Balluff

Annette Feuchtinger

Achim Buck

Rupert Langer

Birgit Luber

Florian Lordick

Horst Zitzelsberger

Michaela Aichler

Axel Walch

Affiliations

Soon will be listed here.

Abstract

Glycosylation in cancer is a highly dynamic process that has a significant impact on tumor biology. Further, the attachment of aberrant glycan forms is already considered a hallmark of the disease state. Mass spectrometry has become a prominent approach to analyzing glycoconjugates. Specifically, matrix-assisted laser desorption/ionisation -mass spectrometric imaging (MALDI-MSI) is a powerful technique that combines mass spectrometry with histology and enables the spatially resolved and label-free detection of glycans. The most common approach to the analysis of glycans is the use of mass spectrometry adjunct to PNGase F digestion and other chemical reactions. In the current study, we perform the analysis of formalin-fixed, paraffin-embedded (FFPE) tissues for natively occurring bioactive glycan fragments without prior digestion or chemical reactions using MALDI-FT-ICR-MSI. We examined 106 primary resected gastric cancer patient tissues in a tissue microarray and correlated native-occurring fragments with clinical endpoints, therapeutic targets such as epidermal growth factor receptor (EGFR) and HER2/neu expressions and the proliferation marker MIB1. The detection of a glycosaminoglycan fragment in tumor stroma regions was determined to be an independent prognostic factor for gastric cancer patients. Native glycan fragments were significantly linked to the expression of EGFR, HER2/neu and MIB1. In conclusion, we are the first to report the detection of native-occurring bioactive glycan fragments in FFPE tissues that influence patient outcomes. These findings highlight the significance of glycan fragments in gastric cancer tumor biology and patient outcome.

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References

Mereiter S, Balmana M, Gomes J, Magalhaes A, Reis C . Glycomic Approaches for the Discovery of Targets in Gastrointestinal Cancer. Front Oncol. 2016; 6:55. PMC: 4783390. DOI: 10.3389/fonc.2016.00055. View

Pinho S, Figueiredo J, Cabral J, Carvalho S, Dourado J, Magalhaes A . E-cadherin and adherens-junctions stability in gastric carcinoma: functional implications of glycosyltransferases involving N-glycan branching biosynthesis, N-acetylglucosaminyltransferases III and V. Biochim Biophys Acta. 2013; 1830(3):2690-700. DOI: 10.1016/j.bbagen.2012.10.021. View

Boscher C, Dennis J, Nabi I . Glycosylation, galectins and cellular signaling. Curr Opin Cell Biol. 2011; 23(4):383-92. DOI: 10.1016/j.ceb.2011.05.001. View

van der Steen S, VAN Tilborg A, Vallen M, Bulten J, van Kuppevelt T, Massuger L . Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11. Gynecol Oncol. 2016; 140(3):527-36. DOI: 10.1016/j.ygyno.2015.12.024. View

Farooqui A . The desulphation of hexosamine sulphates by arylsulphatase B. Experientia. 1976; 32(10):1242-4. DOI: 10.1007/BF01953071. View

Liu D, Shriver Z, Venkataraman G, El Shabrawi Y, Sasisekharan R . Tumor cell surface heparan sulfate as cryptic promoters or inhibitors of tumor growth and metastasis. Proc Natl Acad Sci U S A. 2002; 99(2):568-73. PMC: 117346. DOI: 10.1073/pnas.012578299. View

Hayashi S . Study on the degradation of glycosaminoglycans by canine liver lysosomal enzymes. II. The contributions of hyaluronidase, beta-glucuronidase, sulfatase, and beta-N-acetylhexosaminidase in the case of chondroitin 4-sulfate. J Biochem. 1978; 83(1):149-57. DOI: 10.1093/oxfordjournals.jbchem.a131886. View

Nykopp T, Rilla K, Tammi M, Tammi R, Sironen R, Hamalainen K . Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma. BMC Cancer. 2010; 10:512. PMC: 2956733. DOI: 10.1186/1471-2407-10-512. View

Powers T, Jones E, Betesh L, Romano P, Gao P, Copland J . Matrix assisted laser desorption ionization imaging mass spectrometry workflow for spatial profiling analysis of N-linked glycan expression in tissues. Anal Chem. 2013; 85(20):9799-806. PMC: 3969840. DOI: 10.1021/ac402108x. View

10.

Itzkowitz S, Bloom E, Lau T, Kim Y . Mucin associated Tn and sialosyl-Tn antigen expression in colorectal polyps. Gut. 1992; 33(4):518-23. PMC: 1374070. DOI: 10.1136/gut.33.4.518. View

11.

Raman R, Raguram S, Venkataraman G, Paulson J, Sasisekharan R . Glycomics: an integrated systems approach to structure-function relationships of glycans. Nat Methods. 2005; 2(11):817-24. DOI: 10.1038/nmeth807. View

12.

Auvinen P, Tammi R, Kosma V, Sironen R, Soini Y, Mannermaa A . Increased hyaluronan content and stromal cell CD44 associate with HER2 positivity and poor prognosis in human breast cancer. Int J Cancer. 2012; 132(3):531-9. DOI: 10.1002/ijc.27707. View

13.

Fuster M, Esko J . The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer. 2005; 5(7):526-42. DOI: 10.1038/nrc1649. View

14.

Zhao Y, Nakagawa T, Itoh S, Inamori K, Isaji T, Kariya Y . N-acetylglucosaminyltransferase III antagonizes the effect of N-acetylglucosaminyltransferase V on alpha3beta1 integrin-mediated cell migration. J Biol Chem. 2006; 281(43):32122-30. DOI: 10.1074/jbc.M607274200. View

15.

Berezowska S, Novotny A, Bauer K, Feuchtinger A, Slotta-Huspenina J, Becker K . Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas. PLoS One. 2013; 8(7):e69098. PMC: 3708885. DOI: 10.1371/journal.pone.0069098. View

16.

Heijs B, Holst S, Briaire-de Bruijn I, van Pelt G, de Ru A, Van Veelen P . Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section. Anal Chem. 2016; 88(15):7745-53. DOI: 10.1021/acs.analchem.6b01739. View

17.

Aichler M, Walch A . MALDI Imaging mass spectrometry: current frontiers and perspectives in pathology research and practice. Lab Invest. 2015; 95(4):422-31. DOI: 10.1038/labinvest.2014.156. View

18.

Kearse K, Hart G . Lymphocyte activation induces rapid changes in nuclear and cytoplasmic glycoproteins. Proc Natl Acad Sci U S A. 1991; 88(5):1701-5. PMC: 51092. DOI: 10.1073/pnas.88.5.1701. View

19.

Liu Y, Yen H, Chen C, Chen C, Cheng P, Juan Y . Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc Natl Acad Sci U S A. 2011; 108(28):11332-7. PMC: 3136320. DOI: 10.1073/pnas.1107385108. View

20.

Wu Y, Grabsch H, Ivanova T, Tan I, Murray J, Ooi C . Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer. Gut. 2012; 62(8):1100-11. DOI: 10.1136/gutjnl-2011-301373. View