Overexpression of the phospholipase A2 group V gene in glioma tumors is associated with poor patient prognosis

Figures & data

Table 1 Clinical parameters of LGG patients in TCGA (n=524)

Variable		Number of patients	Percentage of patients
Gender	Male	288	55.0%
	Female	236	45.0%
Age (years)	<41	258	49.2%
	≥41	266	50.8%
WHO Grade	II	254	48.5%
	III	270	51.5%
IDH1 mutation	Yes	388	74.0%
	No	136	26.0%

Abbreviations: IDH1, isocitrate dehydrogenase 1; LGG, low-grade gliomas; TCGA, the Cancer Genome Atlas.

Table 2 Clinical parameters of HGG patients in TCGA (n=523)

Variable		Number of patients	Percentage of patients
Gender	Male	318	60.8%
	Female	205	39.2%
Age (years)	<59	255	48.8%
	≥59	268	51.2%
Chemotherapy	Yes	516	98.7%
	No	7	1.3%
Radiotherapy	Yes	511	97.7%
	No	12	2.3%
IDH1 mutation	Yes	32	6.1%
	No	491	93.2%

Abbreviations: IDH1, isocitrate dehydrogenase 1; HGG, high-grade glioma; TCGA, the Cancer Genome Atlas.

Table 3 Relationship between sPLA2s and patient prognosis in LGGs and HGGs from TCGA database

PLA2Gs	LGG		HGG
Cut-off value	P-value	Cut-off value	P-value
PLA2G1B	0.577	0.8824	0.585	0.0156
PLA2G2A	1.446	0.0068	6.908	0.3268
PLA2G2D	0.930	0.7239	1.324	0.7288
PLA2G2E PLA2G2F PLA2G3 PLA2G4A	NA NA NA 6.799	- - - 0.0017	3.851 3.918 4.571 8.267	0.0061 0.4204 0.0303 0.2306
PLA2G4C	9.100	0.1362	8.568	0.9348
PLA2G4D	0.477	0.4380	0.536	0.0469
PLA2G5	1.338	0.0002	6.447	0.0020
PLA2G6	9.622	<0.0001	8.443	0.8509
PLA2G7	6.167	0.3866	5.562	0.3538
PLA2G10	0.520	0.2176	NA	-
PLA2G12A	9.805	0.1205	9.429	0.3966
PLA2G12B PLA2G15	NA 9.114	- 0.0139	NA 9.575	- 0.2904
PLA2G16	10.030	0.0043	10.26	0.3123

Abbreviations: HGG, high-grade glioma; LGG, low-grade gliomas; NA, not available; TCGA,the Cancer Genome Atlas.

Figure 1 PLA2G5 gene expression was associated with the clinicopathological features of glioma patients(*P<0.05;***P<0.0001). (A) PLA2G5 gene expression was dependent on glioma WHO grade; (B) PLA2G5 gene expression was associated with the histological type of glioma; (C)-(D) PLA2G5 gene expression was positively correlated with patient age in LGGs (P<0.0001) but not in HGGs (P=0.0767); (E)-(F) PLA2G5 gene expression was associated with radiotherapy of HGGs (P=0.0169), but not with chemotherapy (P=0.2771).

Abbreviations: TCGA, the Cancer Genome Atlas; LGG, low-grade glioma; HGG, high-grade glioma; GBM, glioblastoma.

Figure 2 PLA2G5 protein expression in glioma examined by immunohistochemistry. (A)-(D) Immunohistochemical staining images of grade II, III and IV glioma tissues and non-tumor brain tissues (magnification ×200 and ×400); (E) The immunohistochemical score indicates that PLA2G5 protein expression was dependent on WHO grade.

Figure 3 Kaplan-Meier survival analysis based on the median (low and high) PLA2G5 gene transcript expression in glioma. (A) High PLA2G5 gene expression indicated poor survival in LGGs (P=0.0002); (B) High PLA2G5 gene expression indicated poor survival in HGGs (P=0.002).

Abbreviations: TCGA, the Cancer Genome Atlas; LGG, low-grade glioma; HGG, high-grade glioma.

Table 4 Univariate and multivariate Cox regression analyses of PLA2G5 expression and clinicopathological features in affecting the OS of patients with LGG

Variables	Univariate			Multivariate
HR	95% CI	P	HR	95% CI	P
Gender	0.872	0.618–1.232	0.438	0.773	0.543–1.102	0.155
Age	2.914	2.001–4.245	<0.001	2.774	1.857–4.142	<0.001
WHO Grade	3.354	2.296–4.895	<0.001	2.785	1.897–4.089	<0.001
IDH1 mutation	0.294	0.209–0.414	<0.001	0.362	0.252–0.520	<0.001
PLA2G5 expression	1.936	1.363–2.749	<0.001	1.572	1.088–2.274	0.016

Abbreviations: HR, hazard ratio; CI, confidence interval; LGG, low-grade glioma; IDH1, isocitrate dehydrogenase 1; OS, overall survival.

Table 5 Univariate and multivariate Cox regression analyses of PLA2G5 expression and clinicopathological features in affecting the OS of patients with HGG

Variables	Univariate			Multivariate
HR	95% CI	P	HR	95% CI	P
Gender	0.851	0.700–1.034	0.105	0.895	0.735–1.091	0.272
Age	1.862	1.534–2.260	<0.001	1.761	1.447–2.144	<0.001
Chemotherapy	0.581	0.481–0.703	<0.001	0.639	0.517–0.790	<0.001
Radiotherapy	0.537	0.444–0.649	<0.001	0.702	0.567–0.868	0.001
IDH1 mutation	0.308	0.164–0.577	<0.001	0.345	0.182–0.653	0.001
PLA2G5 expression	1.360	1.122–1.649	0.002	1.258	1.032–1.533	0.023

Abbreviations: HR, hazard ratio; CI, confidence interval; HGG, high-grade glioma; IDH1, isocitrate dehydrogenase 1; OS, overall survival.

Figure 4 The relationship between PLA2G5 gene expression and IDH1 status and EMT markers in glioma. (A)-(B) PLA2G5 expression in IDH1 wild-type cases was higher than that in IDH1 mutant cases in both LGGs (p<0.0001) and HGGs (p<0.0001); (C) The correlation between of PLA2G5 and FN1 in HGGs; (D) The correlation between PLA2G5 and VIM in HGGs; (E) The correlation between PLA2G5 and CDH2 in HGGs.

Abbreviations: TCGA, the Cancer Genome Atlas; LGG, low-grade glioma; HGG, high-grade glioma.

Table 6 The correlation of PLA2G5 expression with the expression of EMT markers

EMT markers	LGG		HGG
Pearson’s r	P-value	Pearson’s r	P-value
CDH2	0.1933	<0.0001	0.4545	<0.0001(Figure4E)
VIM	0.2577	<0.0001	0.4052	<0.0001(Figure4D)
FN1	0.07693	0.0785	0.2173	<0.0001(Figure4C)
SNAI1	0.2903	<0.0001	−0.07391	0.0913
SNAI2	0.1239	0.0045	−0.02494	0.5693
TWIST1	0.3166	<0.0001	−0.004144	0.9247
TWIST2	0.2464	<0.0001	NA	-

Abbreviation: EMT, epithelial-mesenchymal transition; LGG, low-grade glioma; HGG, high-grade glioma.

Figure S1 The immunohistochemical staining score of PLA2G5 in glioma and positive/negative control (magnification ×200). (A) Percentage score = 1, intensity score = 1; (B) Percentage score = 2, intensity score = 1; (C) Percentage score = 3, intensity score = 2; (D) Percentage score = 3, intensity score = 3; (E) Positive control: cardiac muscle; (F) Negative control: striated muscle.

Figure S2 Representative MRI images of various glioma subtypes. (A) Glioblastoma (WHO IV); (B) Astrocytoma (WHO III); (C) Astrocytoma (WHO II); (D) Oligodendroglioma (WHO III); (E) Oligodendroglioma (WHO II); (F) Oligoastrocytoma (WHO II).

Figure S3 There was no correlation between the PLA2G5 gene expression level and gender in both LGGs (A) and HGGs (B).

Abbreviations: TCGA, the Cancer Genome Atlas; LGG, low-grade glioma; HGG, high-grade glioma.

Figure S4 Patients with IDH1 mutation survived longer than those with wild-type IDH1 in both LGGs (A) and HGGs (B).

Abbreviations: TCGA, the Cancer Genome Atlas; LGG, low-grade glioma; HGG, high-grade glioma.

Table S1 Clinical parameters of 82 patients form the department of neurosurgery, Xiangya Hospital, Hunan, China

Variable		Number of patients	Percentage of patients
Gender	Male	48	58.5%
	Female	34	41.5%
Age (years)	<50	40	48.8%
	≥50	42	51.2%
WHO Grade	II	23	28.0%
	III	19	23.2%
	IV	40	48.8%