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Ganglioside GM2: a potential biomarker for cholangiocarcinoma.

ABSTRACT: OBJECTIVE:To investigate the expression of glycosphingolipids in serum and tissue from patients with cholangiocarcinoma compared with healthy controls. METHODS:Nanospray ionization-linear ion trap mass spectrometry (NSI-MSn) was used to demonstrate the comparative structural glycomics of glycosphingolipids in serum from patients with cholangiocarcinoma (n=15), compared with healthy controls (n?=?15). GM2 expression in cholangiocarcinoma tissues (n?=?60) was evaluated by immunohistochemistry. RESULTS:Eleven glycosphingolipids were detected by NSI-MSn: CMH (ceramide monohexose), Lac-Cer (galactose (Gal)?1-4 glucose (Glc)?1-1'-ceramide), Gb3 (Gal?1-4Gal?1-4Glc?1-1'-ceramide), Gb4/Lc4 (N-acetylgalactosamine (GalNAc)?1-3Gal?1-4Gal?1-4Glc?1-1'-ceramide/Gal?1-4 N-acetylglucosamine (GlcNAc)?1-3Gal?1-4Glc?1-1'-ceramide), GM3 (N-acetylneuraminic acid (NeuAc)2-3Gal?1-4Glc?1-1'-ceramide), GM2 (GalNAc?1-4[NeuAc2-3]Gal?1-4Glc?1-1'-ceramide), GM1 (Gal?1-3GalNAc?1-4[NeuAc2-3]Gal?1-4Glc?1-1'-ceramide), hFA (hydroxylated fatty acid)-CMH, hFA-Lac-Cer, hFA-Gb3, and hFA-GM3. Lac-Cer was the most abundant structure among the lactosides and globosides (normal, 24.40%?±?0.11%; tumor, 24.61%?±?2.10%), while GM3 predominated among the gangliosides (normal, 29.14%?±?1.31%; tumor, 30.53%?±?4.04%). The two glycosphingolipids that significantly differed between healthy controls and patients with cholangiocarcinoma were Gb3 and GM2. High expression of GM2 was associated with vascular invasion in tissue from patients with cholangiocarcinoma. CONCLUSIONS:Altered expression of glycosphingolipids in tissue and serum from patients with cholangiocarcinoma may contribute to tumor growth and progression. The ganglioside GM2, which significantly increased in the serum of patients with cholangiocarcinoma, represents a promising target as a biomarker for cholangiocarcinoma.

SUBMITTER: Talabnin K

PROVIDER: S-EPMC7375732 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Ganglioside GM2: a potential biomarker for cholangiocarcinoma.

Talabnin Krajang K Talabnin Chutima C Kumagai Tadahiro T Sutatum Nuchanard N Khiaowichit Juthamas J Dechsukhum Chawaboon C Ishihara Mayumi M Azadi Parastoo P Sripa Banchob B

The Journal of international medical research 20200701 7

<h4>Objective</h4>To investigate the expression of glycosphingolipids in serum and tissue from patients with cholangiocarcinoma compared with healthy controls.<h4>Methods</h4>Nanospray ionization-linear ion trap mass spectrometry (NSI-MS<sup>n</sup>) was used to demonstrate the comparative structural glycomics of glycosphingolipids in serum from patients with cholangiocarcinoma (n=15), compared with healthy controls (n = 15). GM2 expression in cholangiocarcinoma tissues (n = 60) was evaluated by ...[more]

PMID: 32692591

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Project description:Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P<0.001), large duct type (P=0.024) and poor histological grade (P=0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P=0.0025), local recurrence-free (P<0.0001) and metastasis-free survival (P<0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P=0.034], disease-specific (HR 2.011; P=0.039), local recurrence-free (HR 2.721; P<0.001) and metastasis-free survival (HR 3.117; P<0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-βsignaling pathway' and 'platelet-derived growth factor receptor-β signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma.

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Ganglioside GM2: a potential biomarker for cholangiocarcinoma.

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Ganglioside GM2: a potential biomarker for cholangiocarcinoma.

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