The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma

Figures & data

Table 1 Clinicopathological Characteristics of HCC Patients

Characteristics		Cases	%
Gender	Female	121	32.4
	Male	253	67.6
Race	Asian	160	44.2
	Black or African American or White	202	55.8
Age (years)	≤60	177	47.5
	>60	196	52.5
Weight (kg)	≤70	184	53.2
	>70	162	46.8
Height (cm)	<170	201	58.9
	≥170	140	41.1
BMI (kg/m^2)	≤25	177	52.5
	>25	160	47.5
AFP (ng/mL)	≤400	215	76.8
	>400	65	23.2
ALB (g/dl)	<3.5	69	23
	≥3.5	231	77
Prothrombin time (sec)	≤4	208	70
	>4	89	30
Child-Pugh grade	A	219	90.9
	B and C	22	9.1
Ishak fibrosis score	0–2	106	49.3
	3–6	109	50.7
T stage	T1 and T2	278	74.9
	T3 and T4	93	25.1
N stage	N0	254	98.4
	N1	4	1.6
M stage	M0	268	98.5
	M1	4	1.5
Pathologic stage	I and II	260	74.3
	III and IV	90	25.7
Residual tumor	R0	327	94.8
	R1 and R2	18	5.2
Histologic grade	G1 and G2	233	63.1
	G3 and G4	136	36.9
Adjacent hepatic tissue inflammation	No	118	49.8
	Yes	119	50.2
Vascular invasion	No	208	65.4
	Yes	110	34.6

Abbreviations: AFP, alpha fetoprotein; ALB, albumin; BMI, body mass index.

Figure 1 CENPQ expression data in hepatocellular carcinoma (HCC). (A) Pan-cancer analysis of CENPQ mRNA expression. (B) CENPQ mRNA expression in HCC cell lines. (C) Analysis of CENPQ mRNA expression in HCC and paired non-cancerous, adjacent tissues. (D) Analysis of CENPQ mRNA expression in HCC and unpaired non-cancerous, adjacent tissues. (E) Analysis of CENPQ mRNA expression in the GEO dataset GSE 98383. (F) Analysis of CENPQ mRNA expression in the GEO dataset GSE 107170. (G) Mean integrated optical density (IOD) values of IHC images of liver and HCC. (H and I) CENPQ protein expression images in normal and HCC. *p < 0.05, **p < 0.01, ***p < 0.001.

Table 2 Correlation Between CENPQ Expression and Clinicopathological Features (Logistic Regression)

Characteristics	Cases	OR (95% CI)	P value
Gender (Male vs Female)	371	1.178 (0.763–1.822)	0.460
Age (years) (>60 vs ≤60)	370	0.555 (0.366–0.837)	0.005
Weight (kg) (>70 vs ≤70)	344	0.483 (0.313–0.741)	< 0.001
BMI (kg/㎡) (>25 vs ≤25)	335	0.643 (0.417–0.989)	0.045
AFP (ng/mL) (>400 vs ≤400)	278	3.243 (1.795–6.075)	< 0.001
ALB (g/dl) (≥3.5 vs <3.5)	297	1.669 (0.969–2.913)	0.067
Prothrombin time (sec) (>4 vs ≤4)	294	0.576 (0.345–0.954)	0.033
Child-Pugh grade (B-C vs A)	239	0.905 (0.368–2.186)	0.825
Ishak fibrosis score (3–6 vs 0–2)	212	1.167 (0.680–2.006)	0.576
T stage (T3-T4 vs T1-T2)	368	1.818 (1.130–2.957)	0.015
N stage (N1 vs N0)	256	2.727 (0.344–55.541)	0.388
M stage (M1 vs M0)	270	2.741 (0.346–55.799)	0.385
Pathologic stage (Stage III–IV vs Stage I–II)	347	2.035 (1.248–3.360)	0.005
Residual tumor (R1-R2 vs R0)	342	1.281 (0.493–3.435)	0.611
Histologic grade (G3-G4 vs G1-G2)	366	2.330 (1.510–3.626)	< 0.001
Adjacent hepatic tissue inflammation (Yes vs No)	234	1.071 (0.641–1.790)	0.794
Vascular invasion (Yes vs No)	315	1.382 (0.868–2.206)	0.173

Abbreviations: ALB, albumin; AFP, alpha fetoprotein; BMI, body mass index; CI, confidence interval; OR, odd ratio. Numbers in bold indicate significant differences at p < 0.05.

Figure 2 Correlation analysis of CENPQ expression and clinicopathological features in HCC. Violin plots summarizing CENPQ expression according to weight (A), BMI (B), age (C), AFP (D), T stage (E), pathologic stage (F), histological grade (G), and prothrombin time (H).

Abbreviations: BMI, body mass index; AFP, alpha fetoprotein; ALB, albumin.

Figure 3 Diagnostic and prognostic value of CENPQ in HCC. (A) ROC analysis indicating good diagnostic performance of CENPQ mRNA profiling in distinguishing HCC samples from normal liver tissue. Kaplan-Meier curves showing the relationship between CENPQ expression and OS (B), DSS (C), and PFI (D). (E–H) Kaplan-Meier curves of OS in subgroups of HCC patients. (E) Age, >60 and ≤60 years, (F) weight, ≤70 and >70 kg, (G) gender, male and female, (H) pathological stage, T2-T4 and T1.

Abbreviations: AUC, area under the ROC curve; CI, 95% confidence interval; OS, overall survival; DSS, disease-specific survival; PFI, progression-free interval.

Figure 4 Univariate and multivariate Cox regression analyses of prognostic-related risk factors. Univariate and multivariate Cox regression analyses of risk factors associated with OS (A), DSS (B), and PFI (C) in HCC.

Abbreviations: OS, overall survival; DSS, disease-specific survival; PFI, progression-free interval.

Figure 5 Identification of CENPQ-related DEGs in HCC and functional and pathway enrichment analyses. (A) Volcano plot of the distribution of DEGs. (B) BP, CC, MF, and KEGG terms for enrichment analysis of DEGs. (C and D) gene set enrichment analysis of DEGs.

Abbreviations: DEGs, differentially expressed genes; GO, gene ontology; BP, biological process; CC, cellular component; MF, molecular function; KEGG, Kyoto Encyclopedia of Genes and Genomes; NES, normalized enrichment score; FDR, false discovery rate.

Figure 6 Correlation analysis of CENPQ expression and immune cell infiltration in HCC. (A) Correlation between CENPQ expression and the abundance of 24 tumor-infiltrating immune cell types. (B) Chord plot depicting the correlation between CENPQ and the abundance of 16 tumor-infiltrating immune cell types. Enrichment scores of positively correlated (C) and negatively correlated (D) immune cells in the CENPQ high and low expression groups.

Abbreviations: Treg, regulatory T cell; Tgd, gamma delta T cell; TFH, T follicular helper cell; Tem, T effector memory cell; DC, dendritic cell; pDC, plasmacytoid DC; NK cell, natural killer cell; iDC, immature DC; aDC, activated DC.

Figure 7 Correlation analysis of CENPQ expression and immune checkpoint genes in HCC. CENPQ was positively correlated with PD-L1 (A), HAVCR2 (B), PD1 (C), CTLA4 (D), SIGLEC15 (E), PDCD1LG2 (F), LAG3 (G) and TIGIT (H). (I) Heat map depicting the correlation of CENPQ with 8 immune checkpoint genes in HCC. *p < 0.05, **p < 0.01, ***p < 0.001.

Figure 8 CENPQ is involved in the regulation of HCC cell cycle and proliferation. (A) Heatmap of the correlation between CENPQ and CDK gene family (CDK1, CDK2, CDK4, CDK6). (B) Heatmap of the correlation between the expression of CENPQ and CCNA, CCNB, CCNC, and CCNE. (C) Expression of CENPQ mRNA in HCC and normal liver tissues. (D) Expression of CENPQ mRNA in HCC cell lines. Silencing of CENPQ in HCC cell lines HUH7 (E) and HEPG2 (F). Flow cytometry was used to detect cycle changes in HUH7 (G) and HEPG2 (H). CCK-8 was used to detect viability changes of HUH7 (I) and HEPG2 (J).*p < 0.05, **p < 0.01, ***p < 0.001.