Serum GM3(d18:1-16:0) and GM3(d18:1-24:1) levels may be associated with lymphoma: An exploratory study with haematological diseases

Abstract

GM3 (monosialodihexosylganglioside) is a type of ganglioside, which is a molecule composed of ceramide and oligosaccharide containing one or more sialic acids. Since GM3 is abundantly expressed in blood cells, we investigated the association between GM3 molecular species and haematological diseases. We measured the serum levels of seven GM3 molecular species in subjects with various haematological diseases (n = 52) and healthy subjects (n = 24) using a liquid chromatography tandem-mass spectrometry technique as an exploratory study. In all the subjects with haematological diseases, GM3(d18:1-16:0) were inversely correlated with the erythrocytes counts. Regarding the difference in serum GM3 molecular species levels among each haematological diseases and healthy subjects, the levels of GM3(d18:1-16:0) and GM3(d18:1-24:1) were higher in the lymphoid neoplasm group than healthy subjects. Principal component analyses also revealed that the GM3(d18:1-16:0) and GM3(d18:1-24:1) levels were significant contributing factors for discriminating the lymphoid neoplasm group. Moreover, in the lymphoid neoplasm group, the GM3(d18:1-16:0) levels were significantly and positively correlated with the levels of C-reactive protein, soluble interleukin-2 receptor, and lactate dehydrogenase. In conclusion, in our exploratory study with haematological diseases, GM3 molecular species showed different distribution among disease groups, and serum GM3(d18:1-16:0) and GM3(d18:1-24:1) might be associated with lymphoma.

Figure 1

Associations between blood test values and GM3 (d18:1-16:0, d18:1-18:0, and d18:1-24:1). Correlations between GM3(d18:1-16:0) and TC (A), RBC (B), and CRP (C); between GM3(d18:1-18:0) and TC (D), RBC(E), and CRP (F); and between GM3(d18:1-24:1) and TC (G), RBC (H), and CRP(I) were observed. Spearman’s rank correlation was used to assess the correlations between the GM3 molecular species and the blood test values. TC, total cholesterol; RBC, erythrocytes; CRP, C-reactive protein.

Figure 2

Concentrations of serum GM3 molecular species according to haematological disease groups. The serum GM3 molecular species were GM3(d18:1-16:0) (A), GM3(d18:1-18:0) (B), GM3(d18:1-20:0) (C), GM3(d18:1-22:0) (D), GM3(d18:1-23:0) (E), GM3(d18:1-24:0) (F), GM3(d18:1-24:1) (G), and total GM3(H). The haematological disease groups were LN (lymphoid neoplasms), MPN (myeloproliferative neoplasms), and immune thrombocytopenia (ITP). The Kruskal-Wallis test followed by the Games Howell test as a post-hoc test were used to compare haematological disease groups and healthy subjects. *P < 0.05, **P < 0.01.

Figure 3

Association between blood test values related to lymphoma and GM3(d18:1-16:0 and d18:1-24:1). Correlations between GM3(d18:1-16:0) and CRP (A), GM3(d18:1-16:0) and sIL-2R (B) and between GM3(d18:1-24:1) and CRP (C), GM3(d18:1-24:1) and sIL-2R (D) were observed. Spearman’s rank correlation was used to assess the correlations between the GM3 molecular species and the blood test values related to lymphoma. CRP, C-reactive protein; sIL-2R, soluble interleukin-2 receptor.

Figure 4

Principal component analysis of serum GM3 molecular species from subjects with haematological diseases and healthy subjects. (A) Scatter plot of principal component analysis scores. Subjects with lymphoid neoplasms were almost clearly separated from the healthy subjects in the t [2] axis direction. (B) Contributing factors to the t [2] axis in the principal component analysis. The GM3(d18:1-16:0) and GM3(d18:1-24:1) levels were significant contributing factors.