Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients, may mediate immune evasion

Table 1 The clinical information of 123 patients with hepatocellular carcinoma

Clinicopathological features	Number	Low expression, n (%)	High expression, n (%)	P value
Age
< 60	68	51 (75.0)	17 (25.0)	0.467
≥ 60	55	40 (72.7)	15 (27.3)
Gender
Male	102	76 (74.5)	26 (25.5)	0.480
Female	21	15 (71.4)	6 (28.6)
Tumor size
≤ 5 cm	65	49 (75.4)	16 (24.6)	0.432
> 5 cm	58	42 (72.4)	16 (27.6)
Cirrhosis
Negative	63	53 (84.1)	10 (15.9)	0.007a
Positive	60	38 (63.3)	22 (36.7)
ALBI score
≤ -2.60	55	40 (72.7)	15 (27.3)	0.001a
> -2.60	68	51 (75.0)	17 (25.0)
APRI score
> 2	38	26 (68.4)	12 (31.6)	0.010a
≤ 2	85	65 (76.5)	20 (23.5)
AFP (ng/mL)
≤ 20	42	36 (85.7)	6 (14.3)	0.025a
> 20	81	55 (67.9)	26 (32.1)
HBV
Negative	12	8 (66.7)	4 (33.3)	0.381
Positive	111	83 (74.8)	28 (25.2)
Intrahepatic metastasis
Negative	111	82 (73.9)	29 (26.1)	0.619
Positive	12	9 (75.0)	3 (25.0)

^aP < 0.05.

ALBI: Albumin-bilirubin; APRI: Aspartate aminotransferase to platelet ratio; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus.

Table 2 Univariate and multivariate Cox regression analysis of overall survival in 123 hepatocellular carcinoma patients

Variables	Overall survival		P value
	HR	95%CI
Univariate analysis
Age	1.320	0.753-2.315	0.332
Gender	0.972	0.678-1.395	0.878
Tumor size	1.168	0.666-2.049	0.588
AFP (ng/mL, ≤ 20/> 20)	1.397	0.771-2.532	0.270
Cirrhosis	2.474	1.376-4.449	0.002b
ALBI score	2.254	1.275-3.975	0.005b
APRI score	1.787	1.014-3.149	0.045a
HBV	0.487	0.217-1.089	0.080
PLXDC1 expression	2.714	1.524-4.832	0.001b
Multivariate analysis
Age	1.273	0.719-2.256	0.408
Gender	1.101	0.753-1.611	0.619
Tumor size	1.128	0.633-1.208	0.683
AFP (ng/mL, ≤ 20/> 20)	0.645	0.324-1.284	0.212
Cirrhosis	0.513	0.219-1.204	0.010a
ALBI score	2.384	1.384-4.217	0.003b
APRI score	1.941	1.096-3.435	0.023a
HBV	0.448	0.196-1.027	0.125
PLXDC1 expression	2.583	1.137-4.993	0.005b

^aP < 0.05.

^bP < 0.01.

CI: Confidence interval; HR: Hazard ratio; ALBI: Albumin-bilirubin; APRI: Aspartate aminotransferase to platelet ratio; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; PLXDC1: Plexin domain-containing 1.

Table 3 Oncogenic pathway parameters in “GSVA” R package enrichment analysis

GeneSet	NES	NOM P value	FDR q-value
WNT_SIGNALING_PATHWAY	1.91	0	0.0054
NOD_LIKE_RECEPTOR_SIGNALING_PATHWAY	1.89	0	0.0057
NEUROTROPHIN_SIGNALING_PATHWAY	1.90	0	0.0058
MAPK_SIGNALING_PATHWAY	1.91	0	0.0061
JAK_STAT_SIGNALING_PATHWAY	1.85	0	0.0069
HEDGEHOG_SIGNALING_PATHWAY	1.87	0	0.0069
TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY	1.84	0	0.0069
TGF_BETA_SIGNALING_PATHWAY	1.84	0	0.0070
CHEMOKINE_SIGNALING_PATHWAY	1.82	0	0.0079

FDR: False detection rate; NES: Normalized Enrichment Score; NOM: Nominal.

Table 4 Immune checkpoints associated with plexin domain-containing 1

Gene	Cor	P value	Gene	Cor	P value
ADORA2A	-0.1481	0.0041	ICOS	0.3617	0
BTLA	0.2724	0	ICOSLG	0.0714	0.1682
CD160	0.2320	0	IL2RA	0.4743	0
CD244	0.1330	0.0100	IL6	0.3618	0
CD274	0.2110	0	IL6R	-0.1707	0.0009
CD96	0.3914	0	KLRC1	0.2157	0
CSF1R	0.4258	0	KLRK1	0.2004	0.0001
CTLA4	0.3953	0	LTA	0.3886	0
HAVCR2	0.5014	0	MICB	0.2998	0
IL10	0.3530	0	NT5E	-0.0069	0.8948
IL10RB	0.3147	0	PVR	0.1524	0.0031
KDR	0.2302	0	RAET1E	0.3120	0
LAG3	0.1047	0.0430	TMIGD2	0.2975	0
LGALS9	0.5536	0	TNFRSF13B	0.2658	0
PDCD1	0.3447	0	TNFRSF13C	0.3396	0
PDCD1LG2	0.2444	0	TNFRSF14	0.2982	0
TGFB1	0.5562	0	TNFRSF17	0.2448	0
TGFBR1	0.4430	0	TNFRSF18	0.4316	0
TIGIT	0.3372	0	TNFRSF25	0.3400	0
VTCN1	0.5346	0	TNFRSF4	0.5544	0
CD27	0.3269	0	TNFRSF8	0.5020	0
CD28	0.2856	0	TNFRSF9	0.3496	0
CD40	0.0859	0.0973	TNFSF13	0.3648	0
CD40LG	0.3333	0	TNFSF13B	0.5252	0
CD48	0.3965	0	TNFSF14	0.1606	0.0018
CD70	0.3658	0	TNFSF15	0.5684	0
CD80	0.4869	0	TNFSF18	0.4378	0
CD86	0.4568	0	TNFSF4	0.3538	0
CXCL12	0.3123	0	TNFSF9	0.3690	0
CXCR4	0.6607	0	ULBP1	0.4382	0
ENTPD1	0.7295	0	KIR2DL1	0.0014	0.9782
HHLA2	0.2502	0	KIR2DL3	0.0596	0.2499

Cor: Correlation.