Core-Fucosylated Tetra-Antennary N-Glycan Containing A Single N-Acetyllactosamine Branch Is Associated with Poor Survival Outcome in Breast Cancer

(1) Glycoproteins account for ~80% of proteins located at the cell surface and in the extracellular matrix. A growing body of evidence indicates that α-L-fucose protein modifications contribute to breast cancer progression and metastatic disease. (2) Using a combination of techniques, including matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) based in cell and on tissue imaging and glycan sequencing using exoglycosidase analysis coupled to hydrophilic interaction ultra-high performance liquid chromatography (HILIC UPLC), we establish that a core-fucosylated tetra-antennary glycan containing a single N-acetyllactosamine (F(6)A4G4Lac1) is associated with poor clinical outcomes in breast cancer, including lymph node metastasis, recurrent disease, and reduced survival. (3) This study is the first to identify a single N-glycan, F(6)A4G4Lac1, as having a correlation with poor clinical outcomes in breast cancer.

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Quantitative hormone receptor (HR) expression and gene expression analysis in HR+ inflammatory breast cancer (IBC) vs non-IBC

10.21203/rs.2.23513/v1 ◽

2020 ◽

Author(s):

Toshiaki Iwase ◽

Kenichi Harano ◽

Hiroko Masuda ◽

Kumiko Kida ◽

Kenneth R. Hess ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Survival Outcome ◽

Stage Iii ◽

Prognostic Role ◽

Poor Survival ◽

Poor Survival Outcome

Abstract Purpose: The purpose of this study was to determine the prognostic role of hormone receptor (HR) on inflammatory breast cancer (IBC) to elucidate its aggressive biological behavior.Methods: We evaluated the expression of estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemical staining and determined the predictive and prognostic role of HR expression on 189 patients with HR+/HER2– IBC and 677 patients with HR+/HER2– stage III non-IBC. Furthermore, we performed gene expression (GE) analyses for 137 patients with HR+/HER2– IBC and 252 patients with corresponding non-IBC to detect genes that are specifically overexpressed in IBC.Results: The expression of ER% was significantly associated with longer distant disease-free survival and overall survival. However, there was no significant relationship between ER% and NAC outcome. In the GE study, 84 genes were identified as significantly distinguishing HR+ IBC from non-IBC. Among the top 15 canonical pathways expressed in IBC, the ERK/MAPK, PDGF, insulin receptor, and IL-7 signaling pathways were associated with the ER signaling pathway. Upregulation of the MYC gene was observed in three of these four pathways. Furthermore, HR+/HER2– IBC had significantly higher MYC amplification, and the genetic alteration was associated with poor survival outcome.Conclusions: Increased HR positivity was significantly associated with improved survival in both HR+/HER2– IBC and HR+/HER2– stage III non-IBC patients. HR+/HER2– IBC had several activated pathways with MYC upregulation, and the genetic alteration was associated with poor survival outcome. The results indicate that MYC may be a key gene for understanding the biology of HR+/HER2– IBC.

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Increased expression of senescence markers p14ARFand p16INK4ain breast cancer is associated with an increased risk of disease recurrence and poor survival outcome

Histopathology ◽

10.1111/his.12948 ◽

2016 ◽

Vol 69 (3) ◽

pp. 479-491 ◽

Cited By ~ 10

Author(s):

Rahmawati Pare ◽

Joo-Shik Shin ◽

Cheok Soon Lee

Keyword(s):

Breast Cancer ◽

Disease Recurrence ◽

Survival Outcome ◽

Poor Survival ◽

Increased Risk ◽

Poor Survival Outcome ◽

Risk Of Disease

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High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer

British Journal of Cancer ◽

10.1038/s41416-019-0662-8 ◽

2019 ◽

Vol 122 (2) ◽

pp. 245-257 ◽

Cited By ~ 4

Author(s):

Masahiro Kawashima ◽

Mariko Tokiwa ◽

Tomomi Nishimura ◽

Yukiko Kawata ◽

Masahiro Sugimoto ◽

...

Keyword(s):

Breast Cancer ◽

Mass Spectrometry ◽

Fatty Acid ◽

Cancer Cells ◽

Immune Checkpoint ◽

Imaging Mass Spectrometry ◽

Invasive Cancer ◽

Fatty Acid Binding ◽

Checkpoint Pathway ◽

Maldi Ims

Abstract Background The fatty acid (FA) composition of phosphatidylinositols (PIs) is tightly regulated in mammalian tissue since its disruption impairs normal cellular functions. We previously found its significant alteration in breast cancer by using matrix-assisted laser desorption and ionisation imaging mass spectrometry (MALDI-IMS). Methods We visualised the histological distribution of PIs containing different FAs in 65 primary breast cancer tissues using MALDI-IMS and investigated its association with clinicopathological features and gene expression profiles. Results Normal ductal cells (n = 7) predominantly accumulated a PI containing polyunsaturated FA (PI-PUFA), PI(18:0/20:4). PI(18:0/20:4) was replaced by PIs containing monounsaturated FA (PIs-MUFA) in all non-invasive cancer cells (n = 12). While 54% of invasive cancer cells (n = 27) also accumulated PIs-MUFA, 46% of invasive cancer cells (n = 23) accumulated the PIs-PUFA, PI(18:0/20:3) and PI(18:0/20:4). The accumulation of PI(18:0/20:3) was associated with higher incidence of lymph node metastasis and activation of the PD-1-related immune checkpoint pathway. Fatty acid-binding protein 7 was identified as a putative molecule controlling PI composition. Conclusions MALDI-IMS identified PI composition associated with invasion and nodal metastasis of breast cancer. The accumulation of PI(18:0/20:3) could affect the PD-1-related immune checkpoint pathway, although its precise mechanism should be further validated.

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Low expression of SLC22A18 predicts poor survival outcome in patients with breast cancer after surgery

Cancer Epidemiology ◽

10.1016/j.canep.2010.09.006 ◽

2011 ◽

Vol 35 (3) ◽

pp. 279-285 ◽

Cited By ~ 10

Author(s):

Hongyu He ◽

Cheng Xu ◽

Ziqin Zhao ◽

Xinyu Qin ◽

Hongmei Xu ◽

...

Keyword(s):

Breast Cancer ◽

Survival Outcome ◽

Poor Survival ◽

Poor Survival Outcome ◽

Low Expression

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Quantitative hormone receptor (HR) expression and gene expression analysis in HR+ inflammatory breast cancer (IBC) vs non-IBC

10.21203/rs.2.23513/v2 ◽

2020 ◽

Author(s):

Toshiaki Iwase ◽

Kenichi Harano ◽

Hiroko Masuda ◽

Kumiko Kida ◽

Kenneth R. Hess ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Survival Outcome ◽

Stage Iii ◽

Prognostic Role ◽

Poor Survival ◽

Poor Survival Outcome

Abstract Background: The purpose of this study was to determine the prognostic role of hormone receptor (HR) on inflammatory breast cancer (IBC) to elucidate its aggressive biological behavior.Methods: We evaluated the expression of estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemical staining and determined the predictive and prognostic role of HR expression on 189 patients with HR+/HER2– IBC and 677 patients with HR+/HER2– stage III non-IBC. Furthermore, we performed gene expression (GE) analyses on 137 patients with HR+/HER2– IBC and 252 patients with HR+/HER2– non-IBC to detect genes that are specifically overexpressed in IBC.Results: The expression of ER% was significantly associated with longer distant disease-free survival and overall survival. However, there was no significant relationship between ER% and neoadjuvant chemotherapy outcome. In the GE study, 84 genes were identified as significantly distinguishing HR+ IBC from non-IBC. Among the top 15 canonical pathways expressed in IBC, the ERK/MAPK, PDGF, insulin receptor, and IL-7 signaling pathways were associated with the ER signaling pathway. Upregulation of the MYC gene was observed in three of these four pathways. Furthermore, HR+/HER2– IBC had significantly higher MYC amplification, and the genetic alteration was associated with poor survival outcome.Conclusions: Higher ER expression was significantly associated with improved survival in both HR+/HER2– IBC and HR+/HER2– stage III non-IBC patients. HR+/HER2– IBC had several activated pathways with MYC upregulation, and the genetic alteration was associated with poor survival outcome. The results indicate that MYC may be a key gene for understanding the biology of HR+/HER2– IBC.

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