Diagnostic and prognostic value of lncRNA cancer susceptibility candidate 9 in hepatocellular carcinoma

Table 1 Baseline analysis, n (%)

Factors		Patient group (n = 80)	Control group (n = 50)	χ2 /t	P value
Gender				0.264	0.609
	Male	50 (62.50)	29(58.00)
	Female	30 (37.50)	21 (42.00)
Age (yr)		54.6 ± 5.0	53.7 ± 4.1	1.068	0.288
BMI (kg/m2)		22.86 ± 1.93	23.17 ± 2.07	0.866	0.388
Past medical history
	Hypertension	25 (31.25)	10 (20.00)	1.979	0.160
	Hyperlipidemia	13 (16.25)	6 (12.00)	0.445	0.505
	Diabetes	20 (25.00)	10 (20.00)	0.433	0.510
Smoking history				0.081	0.776
	Yes	50 (62.50)	30 (60.00)
	No	30 (37.50)	20 (40.00)
History of alcoholism				0.494	0.482
	Yes	15 (18.75)	7 (14.00)
	No	65 (81.25)	43 (86.00)
Place of residence				0.177	0.674
	Urban area	45 (56.25)	30 (60.00)
	Rural area	35 (43.75)	20 (40.00)
Tumor size
	≥ 5 cm	45 (56.25)
	< 5 cm	35 (43.75)
Combined hepatitis
	Yes	70 (87.50)
	No	10 (12.50)
TNM staging
	Stage I+II	33 (41.25)
	Stage III+IV	47 (58.75)
Lymph node metastasis
	Yes	42 (52.50)
	No	38 (47.50)
Differentiation
	Low differentiation	27 (33.75)
	Moderate + high differentiation	53 (66.25)
AFP (ng/mL)				59.583	< 0.001
	≤ 200	25 (31.25)	50 (100.00)
	>200	55 (68.75)	0 (0.00)

BMI: Body mass index; AFP: Alpha fetoprotein; TNM: Tumor, node, metastasis.

Table 2 Relationship between cancer susceptibility candidate 9 and pathological data

Factors		Patient group (n = 80)	T	P value
Gender			0.308	0.759
	Male (n = 50)	3.287 ± 0.553
	Female (n = 30)	3.326 ± 0.553
Age (yr)			0751	0.455
	< 55 (n = 35)	3.354 ± 0.504
	≥ 55 (n = 45)	3.261 ± 0.585
Tumor size			4.357	< 0.001
	≥ 5 cm (n = 45)	3.489 ± 0.414
	< 5 cm (n = 35)	3.06 ± 0.611
Combined hepatitis			0.575	0.567
	Yes (n = 70)	3.315 ± 0.540
	No (n = 10)	3.208 ± 0.634
TNM stage			4.157	< 0.001
	Stage I+II (n = 33)	3.496 ± 0.448
	Stage III+IV (n = 47)	3.024 ± 0.567
Lymph node metastasis			4.557	< 0.001
	Yes (n = 42)	3.54 ± 0.445
	No (n = 38)	3.038 ± 0.538
Differentiation			4.387	< 0.001
	Low differentiation (n = 27)	3.642 ± 0.405
	Moderate + high differentiation (n = 53)	3.128 ± 0.535
AFP (ng/mL)			3.617	0.001
	≤ 200 (n = 25)	3.609 ± 0.393
	> 200 (n = 55)	3.162 ± 0.557

AFP: Alpha fetoprotein; TNM: Tumor, node, metastasis.

Table 3 Receiver operating characteristic parameters

Factors	HCC diagnosis	Tumor size	TNM stage	Lymph node metastasis	Differentiation	AFP
AUC	0.933	0.726	0.743	0.752	0.777	0.738
SD	0.026	0.060	0.059	0.055	0.051	0.054
95%CI	0.882-0.983	0.608-0.845	0.628-0.858	0.645-0.859	0.678-0.876	0.632-0.844
P value	< 0.001	0.001	< 0.001	< 0.001	< 0.001	0.001
Specificity	87.50%	95.56%	48.48%	88.10%	92.59%	100.00%
Sensitivity	90.00%	48.57%	93.62%	52.63%	52.83%	45.45%
Youden index	77.50%	44.13%	42.10%	40.73%	45.42%	45.45%
Cut-off	< 2.672	< 2.916	> 2.919	< 3.057	< 3.148	< 3.057

AUC: Area under curve; HCC: Hepatocellular carcinoma; AFP: Alpha fetoprotein.

Table 4 Multivariate Cox regression analysis

Factors	Univariate Cox			Multivariate Cox
	P value	HR	95%CI	P value	HR	95%CI
Gender (male vs female)	0.272	1.320	1.320-0.804
Age (< 55 yr vs ≥ 55 yr)	0.438	0.825	0.825-0.508
Tumor size (≥ 5 cm vs < 5 cm)	0.952	1.015	1.015-0.624
Combined hepatitis (yes vs no)	0.636	1.185	1.185-0.586
TNM staging (stage I+II vs stage III+IV)	0.000	4.271	4.271-2.391	0.006	2.501	1.308-4.781
Lymph node metastasis (yes vs no)	0.001	0.428	0.428-0.259	0.025	0.535	0.309-0.924
Differentiation (low vs medium + high)	0.000	0.242	0.242-0.144	0.000	0.326	0.186-0.569
AFP (≤ 200 vs > 200 ng/mL)	0.025	1.914	1.914-1.086	0.042	1.935	1.023-3.662
CASC9 (< 3.305 vs ≥ 3.305)	0.005	2.023	2.023-1.235	0.021	2.024	1.112-3.682

AFP: Alpha fetoprotein; TNM: Tumor, node, metastasis; CASC9: Cancer susceptibility candidate 9.

Table 5 The top 10 Gene Ontology enrichment functions

Term	Count	P value	Genes
Negative regulation of transcription from the RNA polymerase II promoter	9	0.001	PHF19, SQSTM1, CPEB3, E2F7, ESR1, CBX2, SOX6, HMGA2, TWIST1
Positive regulation of transcription regulatory region DNA binding	3	0.002	WNT3A, HMGA2, TWIST1
Cytoplasm	27	0.003	CLSPN, CPEB3, TPM2, BDNF, RNF165, MAPT, STRIP2, HOXA10, FASN, PLCB1, CDC37L1, ARL2, IRAK1, SGK1, MAP2K1, KIF5A, DDX39B, PIM1, SOCS6, ESR1, SNAI2, WEE1, CDC25A, ADM, CA8, PSAT1, DUSP6
Positive regulation of transcription, DNA-templated	6	0.009	RET, MAP2K1, FOXK1, MYRF, ESR1, PLCB1
Osteoblast differentiation	4	0.010	WNT3A, FASN, SNAI2, TWIST1
Neuron projection morphogenesis	3	0.011	BDNF, SGK1, WEE1
Transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific	5	0.019	PLAG1, HOXA10, ESR1, HMGA2, MYBL2
Negative regulation of sequence-specific DNA binding transcription factor activity	3	0.021	PIM1, ESR1, TWIST1
Neuron projection	4	0.027	CPEB3, KIF5A, MAPT, SLC6A4

PHF19: PHD finger protein 19; SQSTM1: Sequestosome 1; CPEB3: Cytoplasmic polyadenylation element binding protein 3; E2F7: E2F transcription factor 7; ESR1: Estrogen receptor 1; CBX2: Chromobox 2; SOX6: SRY-box transcription factor 6; HMGA2: High mobility group AT-hook 2; TWIST1: Twist family bHLH transcription factor 1; WNT3A: Wnt family member 3A; CLSPN: Claspin; TPM2: Tropomyosin 2; BDNF: Brain derived neurotrophic factor; RNF165: Ring finger protein 165; MAPT: Microtubule associated protein tau; STRIP2: Striatin interacting protein 2; HOXA10: Homeobox A10; FASN: Fatty acid synthase; PLCB1: Phospholipase C beta 1; CDC37L1: Cell division cycle 37 like 1; ARL2: ADP ribosylation factor like GTPase 2; IRAK1: Interleukin 1 receptor associated kinase 1; SGK1: Serum/glucocorticoid regulated kinase 1; MAP2K1: Mitogen-activated protein kinase kinase 1; KIF5A: Kinesin family member 5A; DDX39B: DExD-box helicase 39B; PIM1: Pim-1 proto-oncogene, serine/threonine kinase; SOCS6: Suppressor of cytokine signaling 6; SNAI2: Snail family transcriptional repressor 2; WEE1: WEE1 G2 checkpoint kinase; CDC25A: Cell division cycle 25A; ADM: Adrenomedullin; CA8: Carbonic anhydrase 8; PSAT1: Phosphoserine aminotransferase 1; DUSP6: Dual specificity phosphatase 6; RET: Ret proto-oncogene; FOXK1: Forkhead box K1; MYRF: Myelin regulatory factor; PLAG1: PLAG1 zinc finger; MYBL2: MYB proto-oncogene like 2; SLC6A4: Solute carrier family 6 member 4.

Table 6 The top10 Kyoto Encyclopedia of Genes and Genomes signal pathways

Term	Count	P value	Genes
MicroRNAs in cancer	7	0.002	KIF23, CCNE1, MAP2K1, WNT3A, PIM1, HMGA2, CDC25A
Pathways in cancer	8	0.005	CCNE1, RET, MAP2K1, WNT3A, ITGA2, LAMC1, AXIN2, PLCB1
p53 signaling pathway	4	0.007	STEAP3, CCNE1, SERPINE1, CHEK1
Chagas disease (American trypanosomiasis)	4	0.024	GNAL, IRAK1, SERPINE1, PLCB1
Proteoglycans in cancer	5	0.024	MAP2K1, WNT3A, ESR1, ITGA2, TWIST1
Cell cycle	4	0.030	CCNE1, CHEK1, WEE1, CDC25A
PI3K-Akt signaling pathway	6	0.038	CCNE1, SGK1, MAP2K1, ITGA2, LAMC1, ANGPT2
Hippo signaling pathway	4	0.048	WNT3A, SERPINE1, AXIN2, SNAI2
Small cell lung cancer	3	0.081	CCNE1, ITGA2, LAMC1
Progesterone-mediated oocyte maturation	3	0.082	MAP2K1, CPEB3, CDC25A

KIF23: Kinesin family member 23; CCNE1: Cyclin E1; MAP2K1: Mitogen-activated protein kinase kinase 1; WNT3A: Wnt family member 3A; PIM1: Pim-1 proto-oncogene, serine/threonine kinase; HMGA2: High mobility group AT-hook 2; CDC25A: Cell division cycle 25A; RET: Ret proto-oncogene; ITGA2: Integrin subunit alpha 2; LAMC1: Laminin subunit gamma 1; AXIN2: Axin 2; PLCB1: Phospholipase C beta 1; STEAP3: STEAP3 metalloreductase; SERPINE1: Serpin family E member 1; CHEK1: Checkpoint kinase 1; CPEB3: Cytoplasmic polyadenylation element binding protein 3; SGK1: Serum/glucocorticoid regulated kinase 1; ANGPT2: Angiopoietin 2; WEE1: WEE1 G2 checkpoint kinase; ESR1: Estrogen receptor 1; TWIST1: Twist family bHLH transcription factor 1; GNAL: G protein subunit alpha L; IRAK1: Interleukin 1 receptor associated kinase 1; SNAI2: Snail family transcriptional repressor 2.