Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies to date. The impressively developed stroma that surrounds and modulates the behavior of cancer cells is one of the main factors regulating the PDAC growth, metastasis and therapy resistance. Here, w...

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Autores principales:	Na Sun, Marija Trajkovic-Arsic, Fengxia Li, Yin Wu, Corinna Münch, Thomas Kunzke, Annette Feuchtinger, Katja Steiger, Anna Melissa Schlitter, Wilko Weichert, Irene Esposito, Jens T. Siveke, Axel Walch
Formato:	article
Lenguaje:	EN
Publicado:	SpringerOpen 2021
Materias:	MALDI-FT-ICR-MSI Glycans PDAC Medical physics. Medical radiology. Nuclear medicine R895-920
Acceso en línea:	https://doaj.org/article/96cfb2d53afd4a988f9ac1824437c7b2
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spelling	oai:doaj.org-article:96cfb2d53afd4a988f9ac1824437c7b22021-12-05T12:11:04ZNative glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma10.1186/s13550-021-00862-y2191-219Xhttps://doaj.org/article/96cfb2d53afd4a988f9ac1824437c7b22021-12-01T00:00:00Zhttps://doi.org/10.1186/s13550-021-00862-yhttps://doaj.org/toc/2191-219XAbstract Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies to date. The impressively developed stroma that surrounds and modulates the behavior of cancer cells is one of the main factors regulating the PDAC growth, metastasis and therapy resistance. Here, we postulate that stromal and cancer cell compartments differentiate in protein/lipid glycosylation patterns and analyze differences in glycan fragments in those compartments with clinicopathologic correlates. Results We analyzed native glycan fragments in 109 human FFPE PDAC samples using high mass resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometric imaging (MALDI-FT-ICR-MSI). Our method allows detection of native glycan fragments without previous digestion with PNGase or any other biochemical reaction. With this method, 8 and 18 native glycans were identified as uniquely expressed in only stromal or only cancer cell compartment, respectively. Kaplan–Meier survival model identified glycan fragments that are expressed in cancer cell or stromal compartment and significantly associated with patient outcome. Among cancer cell region-specific glycans, 10 predicted better and 6 worse patient survival. In the stroma, 1 glycan predicted good and 4 poor patient survival. Using factor analysis as a dimension reduction method, we were able to group the identified glycans in 2 factors. Multivariate analysis revealed that these factors can be used as independent survival prognostic elements with regard to the established Union for International Cancer Control (UICC) classification both in tumor and stroma regions. Conclusion Our method allows in situ detection of naturally occurring glycans in FFPE samples of human PDAC tissue and highlights the differences among glycans found in stromal and cancer cell compartment offering a basis for further exploration on the role of specific glycans in cancer–stroma communication.Na SunMarija Trajkovic-ArsicFengxia LiYin WuCorinna MünchThomas KunzkeAnnette FeuchtingerKatja SteigerAnna Melissa SchlitterWilko WeichertIrene EspositoJens T. SivekeAxel WalchSpringerOpenarticleMALDI-FT-ICR-MSIGlycansPDACMedical physics. Medical radiology. Nuclear medicineR895-920ENEJNMMI Research, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MALDI-FT-ICR-MSI Glycans PDAC Medical physics. Medical radiology. Nuclear medicine R895-920
spellingShingle	MALDI-FT-ICR-MSI Glycans PDAC Medical physics. Medical radiology. Nuclear medicine R895-920 Na Sun Marija Trajkovic-Arsic Fengxia Li Yin Wu Corinna Münch Thomas Kunzke Annette Feuchtinger Katja Steiger Anna Melissa Schlitter Wilko Weichert Irene Esposito Jens T. Siveke Axel Walch Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
description	Abstract Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies to date. The impressively developed stroma that surrounds and modulates the behavior of cancer cells is one of the main factors regulating the PDAC growth, metastasis and therapy resistance. Here, we postulate that stromal and cancer cell compartments differentiate in protein/lipid glycosylation patterns and analyze differences in glycan fragments in those compartments with clinicopathologic correlates. Results We analyzed native glycan fragments in 109 human FFPE PDAC samples using high mass resolution matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometric imaging (MALDI-FT-ICR-MSI). Our method allows detection of native glycan fragments without previous digestion with PNGase or any other biochemical reaction. With this method, 8 and 18 native glycans were identified as uniquely expressed in only stromal or only cancer cell compartment, respectively. Kaplan–Meier survival model identified glycan fragments that are expressed in cancer cell or stromal compartment and significantly associated with patient outcome. Among cancer cell region-specific glycans, 10 predicted better and 6 worse patient survival. In the stroma, 1 glycan predicted good and 4 poor patient survival. Using factor analysis as a dimension reduction method, we were able to group the identified glycans in 2 factors. Multivariate analysis revealed that these factors can be used as independent survival prognostic elements with regard to the established Union for International Cancer Control (UICC) classification both in tumor and stroma regions. Conclusion Our method allows in situ detection of naturally occurring glycans in FFPE samples of human PDAC tissue and highlights the differences among glycans found in stromal and cancer cell compartment offering a basis for further exploration on the role of specific glycans in cancer–stroma communication.
format	article
author	Na Sun Marija Trajkovic-Arsic Fengxia Li Yin Wu Corinna Münch Thomas Kunzke Annette Feuchtinger Katja Steiger Anna Melissa Schlitter Wilko Weichert Irene Esposito Jens T. Siveke Axel Walch
author_facet	Na Sun Marija Trajkovic-Arsic Fengxia Li Yin Wu Corinna Münch Thomas Kunzke Annette Feuchtinger Katja Steiger Anna Melissa Schlitter Wilko Weichert Irene Esposito Jens T. Siveke Axel Walch
author_sort	Na Sun
title	Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
title_short	Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
title_full	Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
title_fullStr	Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
title_full_unstemmed	Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
title_sort	native glycan fragments detected by maldi mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma
publisher	SpringerOpen
publishDate	2021
url	https://doaj.org/article/96cfb2d53afd4a988f9ac1824437c7b2
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Native glycan fragments detected by MALDI mass spectrometry imaging are independent prognostic factors in pancreatic ductal adenocarcinoma

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