Open AccessN ‐glycan signatures identified in tumor interstitial fluid and serum of breast cancer patients: association with tumor biology and clinical outcome
Author(s) -
Terkelsen Thilde,
Haakensen Vilde D.,
Saldova Radka,
Gromov Pavel,
Hansen Merete Kjær,
Stöckmann Henning,
Lingjærde Ole Christian,
BørresenDale AnneLise,
Papaleo Elena,
Helland Åslaug,
Rudd Pauline M.,
Gromova Irina
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12312
Subject(s) - glycan , breast cancer , glycoprotein , breast tumor , cancer , tumor microenvironment , cancer research , medicine , biology , oncology , pathology , microbiology and biotechnology
Particular N ‐glycan structures are known to be associated with breast malignancies by coordinating various regulatory events within the tumor and corresponding microenvironment, thus implying that N ‐glycan patterns may be used for cancer stratification and as predictive or prognostic biomarkers. However, the association between N ‐glycans secreted by breast tumor and corresponding clinical relevance remain to be elucidated. We profiled N ‐glycans by HILIC UPLC across a discovery dataset composed of tumor interstitial fluids ( TIF , n = 85), paired normal interstitial fluids ( NIF , n = 54) and serum samples ( n = 28) followed by independent evaluation, with the ultimate goal of identifying tumor‐related N ‐glycan patterns in blood of patients with breast cancer. The segregation of N ‐linked oligosaccharides revealed 33 compositions, which exhibited differential abundances between TIF and NIF . TIF s were depleted of bisecting N ‐glycans, which are known to play essential roles in tumor suppression. An increased level of simple high mannose N ‐glycans in TIF strongly correlated with the presence of tumor infiltrating lymphocytes within tumor. At the same time, a low level of highly complex N ‐glycans in TIF inversely correlated with the presence of infiltrating lymphocytes within tumor. Survival analysis showed that patients exhibiting increased TIF abundance of GP 24 had better outcomes, whereas low levels of GP 10, GP 23, GP 38, and coreF were associated with poor prognosis. Levels of GP 1, GP 8, GP 9, GP 14, GP 23, GP 28, GP 37, GP 38, and coreF were significantly correlated between TIF and paired serum samples. Cross‐validation analysis using an independent serum dataset supported the observed correlation between TIF and serum, for five of nine N ‐glycan groups: GP 8, GP 9, GP 14, GP 23, and coreF. Collectively, our results imply that profiling of N ‐glycans from proximal breast tumor fluids is a promising strategy for determining tumor‐derived glyco‐signature(s) in the blood. N ‐glycans structures validated in our study may serve as novel biomarkers to improve the diagnostic and prognostic stratification of patients with breast cancer.