Expression and Prognostic Value Identification of Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) in Brain Low-Grade Glioma

Figures & data

Figure 1 The mRNA expression analysis of MTHFD2. (A) MTHFD2 expression profile across all tumor samples and normal tissues with dot plot. Red: MTHFD2 high expression in cancer tissues. Green: MTHFD2 low expression in cancer tissues. Black: No difference between tumor and normal tissues. Red box indicates LGG. (B) MTHFD2 differential expression in normal and LGG samples. Detailed MTHFD2 expression among LGG patients was assessed using GSE60898 dataset based on (C) Age, (D) BRAF genetic status, (E) Locations, (F) Primary or recurrent tumor, and (G) Primary tumor that further progressed.

Table 1 The Clinical Characteristics of LGG Patients in TCGA Lower Grade Glioma (LGG) Cohort

Characteristics		Sample Size	Mean±SE	P
Age	<45	177	4.298±0.085	0.321
	≥45	80	4.149±0.118
Subtypes	Astrocytoma	65	4.117±0.139	0.478
	Oligodendroglioma	114	4.328±0.104
	Mixed glioma	78	4.254±0.124
Radiation therapy	No	132	4.403±0.094	0.238
	Yes	93	4.232±0.108
Gender	Male	137	4.215±0.091	0.566
	Female	120	4.295±0.106
IDH1 mutation tested	No	150	4.172±0.087	0.017
	Yes	59	4.572±0.144
Pharmaceutical therapy	No	41	4.255±0.176	0.367
	Yes	45	4.455±0.134

Figure 2 The association analysis of MTHFD2 mRNA expression with clinical phenotypes of patients using TCGA-LGG data. (A) Age. (B) Gender. (C) Tumor subtypes. (D) IDH mutation status. (E) Pharmaceutical therapy. (F) Radiation therapy.

Figure 3 The MTHFD2 expression analysis. (A) Brain mRNA expression. (B) Representative immunohistochemical images of MTHFD2 in normal and LGG tissues. (C) Subcellular location of MTHFD2 protein in human and mouse cancer cells.

Figure 4 The association of MTHFD2 expression with overall survival of LGG patients.

Table 2 Restrict Survival Analysis on LGG Patients in TCGA Lower Grade Glioma (LGG) Cohort

		Low/High	HR (95% CI)	P
Pharmaceutical therapy	No	20/21	2.026 (0.464, 8.842)	0.182
	Yes	23/23	1.052 (0.471, 2.351)	0.898
IDH1 mutation tested	No	76/76	1.492 (0.692, 3.218)	0.275
	Yes	30/30	2.086 (0.540, 8.051)	0.324
Radiation therapy	No	67/67	1.687 (0.541, 5.252)	0.384
	Yes	47/47	1.705 (0.778, 3.732)	0.1422
Gender	Male	70/69	2.023 (0.844, 4.849)	0.096
	Female	60/61	1.220 (0.534, 2.786)	0.624
Subtypes	Astrocytoma	33/33	2.077 (0.539, 8.005)	0.243
	Oligodendroglioma	58/58	1.175 (0.496, 2.784)	0.706
	Mixed glioma	39/39	1.047 (0.331, 3.301)	0.934
Age	<45 years old	89/90	1.260 (0.642, 2.470)	0.493
	≥45 years old	40/41	4.530 (1.066, 19.25)	0.040

Table 3 Multivariate Cox Regression Analysis on LGG Patients

Parameters	Wald	HR (95% CI)	P
Pharmaceutical therapy	1.409	1.787 (0.685, 4.660)	0.235
IDH1 mutation tested	0.123	1.276 (0.327, 4.974)	0.725
Radiation therapy	2.814	2.628 (0.850, 8.128)	0.093
Gender	0.933	0.646 (0.266, 1.569)	0.334
Subtypes	1.381	1.626 (0.723, 3.656)	0.240
Age	0.781	1.755 (0.504, 6.111)	0.377
MTHFD2	2.609	2.033 (0.806, 4.806)	0.106

Figure 5 The enriched biological process of 175 co-expressed genes with MTHFD2.

Figure 6 Potential enriched KEGG pathways of 175 co-expressed genes with MTHFD2. (A) The top 8 significant pathways. **P<0.01. (B) Interaction between pathway and related genes.

Figure 7 The GSEA analysis on MTHFD2 in LGG. (A) One carbon pool by folate pathway positively associated with MTHFD2. (B) Pathway plot of one carbon pool by folate pathway. The numbers mean the enzyme code (EC). For example, EC: 1.5.1.3 represents dihydrofolate reductase.

Figure 8 Tumor-immune system interaction analysis on MTHFD2. (A) Associations between MTHFD2 expression and immune subtypes in LGG. (B) Associations between MTHFD2 expression and molecular subtypes in LGG.