Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer

Table 1 Clinical characteristic of 497 patients with papillary thyroid cancer

Variable	Train cohort	Test cohort	P value
	(n = 249)	(n = 248)
Age			0.968
< 45	112	112
≥ 45	137	138
Sex			0.064
Male	75	57
Female	174	193
Vital status			0.617
Death	9	7
Alive	240	241
Stages			0.768
I	140	138
II	28	23
III	53	61
IV	28	26
T classification			0.302
T1	67	76
T2	92	74
T3	78	85
T4	12	11
Tx	0	2
N classification			0.166
N0	107	121
N1	120	99
Nx	22	28
M classification			0.584
M0	139	139
M1	3	6
Mx	107	103

Table 2 Univariate cox regression analyses of microRNA were distinctly associated with overall survival of papillary thyroid cancer in train cohort

miRNA	P value	HR	Lower 95%CI	Upper 95%CI
hsa-miR-138-5p	0.0001	1.0024	1.0011	1.0036
hsa-miR-1179	0.0006	1.0120	1.0050	1.0191
hsa-miR-138-1-3p	0.0009	1.0280	1.0112	1.0451
hsa-miR-612	0.0064	1.3720	1.0929	1.7222
hsa-miR-7-2-3p	0.0077	1.0109	1.0028	1.0191
hsa-miR-146b-3p	0.0165	0.9999	0.9998	0.9999
hsa-miR-181a-2-3p	0.0177	0.9999	0.9998	0.9999
hsa-miR-146b-5p	0.0224	0.9999	0.9999	0.9999
hsa-miR-5682	0.0308	1.8605	1.0587	3.2696
hsa-miR-31-5p	0.0320	0.9952	0.9908	0.9995
hsa-miR-424-3p	0.0393	0.9790	0.9594	0.9989
hsa-miR-6842-3p	0.0437	0.9457	0.8959	0.9984
hsa-miR-4709-3p	0.0471	0.9702	0.9416	0.9996

CI: Confidence interval; HR: Hazard ratio.

Table 3 Multivariate cox regression analyses of microRNA were distinctly associated with overall survival of papillary thyroid cancer in train cohort

miRNA	Coefficient	P value	HR	Lower 95%CI	Upper 95%CI
hsa-miR-181a-2-3p	-0.001	0.0800	1.000	1.000	1.000
hsa-miR-138-5p	0.003	0.0001	1.003	1.001	1.004
hsa-miR-424-3p	-0.018	0.0590	0.982	0.964	1.001
hsa-miR-612	0.284	0.0242	1.329	1.038	1.702

CI: Confidence interval; HR: Hazard ratio.

Table 4 Univariate and multivariate cox regression analyses of the four miRNA signature and clinicopathologic factors in the entire set

	Univariate analysis		Multivariate analysis
	HR (95%CI)	P	HR (95%CI)	P
Age (< 45 vs ≥ 45)	0.013 (0.000-0.756)	0.036	-	-
Stage (I/II vs III/IV)	0.141 (0.045-0.439)	0.001	-	-
Sex	2.029 (0.734-5.613)	0.173	-	-
Four miRNA signature (high risk vs low risk)	8.625 (1.956-38.03)	0.004	6.186 (1.405-27.24)	0.016

CI: Confidence interval; HR: Hazard ratio.

Table 5 The significant enriched Gene Ontology biological processes of target genes

Term	Count	Fold enrichment	P value
Regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism	291	1.228	< 0.001
Transport	127	1.247	0.005
Regulation of gene expression, epigenetic	12	2.171	0.008
Cell adhesion	12	2.653	0.001

Table 6 The significant enriched Kyoto Encyclopedia of Genes and Genomes pathways of target genes

Term	Count	Fold enrichment	P value
Integrin family cell surface interactions	149	1.265	< 0.001
Beta1 integrin cell surface interactions	147	1.273	< 0.001
Proteoglycan syndecan-mediated signaling events	146	1.267	< 0.001
PAR1-mediated thrombin signaling events	145	1.306	< 0.001
Thrombin/PAR pathway	145	1.305	< 0.001
VEGF and VEGFR signaling network	145	1.301	< 0.001
Alpha9 beta1 integrin signaling events	145	1.300	< 0.001
ErbB receptor signaling network	145	1.294	< 0.001
S1P pathway	145	1.294	< 0.001
TRAIL signaling pathway	145	1.277	< 0.001

PAR: Protease-activated receptor; VEGF: Vascular endothelial-derived growth factor; SIP: Sphingosine 1-phosphate; TRAIL: Tumour necrosis factor-related apoptosis-inducing ligand.