High Platelet Count is a Potential Prognostic Factor of the Early Recurrence of Hepatocellular Carcinoma in the Presence of Circulating Tumor Cells

Figures & data

Table 1 Clinical Characteristics of the Hepatocellular Carcinoma Patients in the Study

Characteristics	Values
Patients, n	127
Sex (male)	108 (85.0%)
Age, year (≥45)	72 (56.7%)
BMI (≥24kg/m^2)	43 (33.9%)
Diabetes mellitus	10 (7.9%)
HBsAg (positive)	115 (80.6%)
HBV-DNA(≥5×10^2 IU/mL)	89 (70.1%)
Child-Pugh class (A stage)	121 (95.3%)
Total bilirubin (≥17.1 µmol/L)	40 (31.5%)
ALB (≥35 mg/L)	111 (87.4%)
ALT (≥40 U/L)	59 (46.5%)
AST (≥40 U/L)	67 (52.8%)
PT (≥13 s)	62 (48.8%)
INR (≥1)	98 (77.2%)
Platelet count (≥225×10^9/L)	61 (48.0%)
CTCs (>5/5 mL)	77 (60.6%)
AFP (≥200 µg/mL)	76 (59.8%)
Tumor size (≥5 cm)	88 (69.3%)
Multiple lesions (yes)	37 (29.1%)
Inflow blood occlusion (yes)	95 (74.8%)
Tumor capsule (complete)	100 (78.7%)
Resection margin (≥1cm)	38 (78.7%)
MVI (positive)	79 (62.2%)
Histological grade (≥3)	69 (54.3%)
Histological cirrhosis (yes)	48 (37.8%)
Satellite nodule (yes)	27 (21.3%)
Ki67 (≥35%)	59 (46.5%)
Postoperative adjuvant therapy (yes)	55 (43.3%)

Note: Values shown are n (%).

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CTCs, circulating tumor cells; HBV-DNA, hepatitis B virus DNA; HBsAg, hepatitis B surface antigen; INR, international normalized ratio; MVI, microvascular invasion; PT, prothrombin time.

Figure 1 Correlation between preoperative CTC count and platelet count. (A) Distribution of CTCs in the patients with platelet count ≥225×109/L and platelet count <225×109/L. (B) Analysis of the distribution of CTCs in subgroups of patients. ***P < 0.001.

Figure 2 Kaplan–Meier survival curves of early recurrence-free survival (RFS) after liver resection in the patients stratified by preoperative (A) circulating tumor cells (CTCs) and (B) Platelet.

Figure 3 Kaplan–Meier survival curves of early RFS for the subgroup patients stratified by preoperative (A) CTCs and (B) Platelet.

Table 2 Univariate and Multivariate Analyses of Prognostic Factors Associated with the Early Recurrence of HCC

Characteristic	Comparison	Univariate			Multivariate
		HR	95% CI	P-value	HR	95% CI	P-value
Sex	Male vs female	0.990	0.536–1.829	0.975
Age, year	≥45 vs <45	0.738	0.477–1.142	0.173
BMI, kg/m^2	≥24 vs <24	0.543	0.330–0.894	0.016	0.908	0.514–1.601	0.738
Diabetes mellitus	Yes vs no	0.681	0.275–1.683	0.405
HBsAg	Positive vs negative	1.256	0.578–2.727	0.565
HBV-DNA, 10^2 IU/mL	≥5 vs <5	0.963	0.604–1.536	0.874
Child-Pugh class	A stage vs B stage	1.071	0.337–3.397	0.908
Total bilirubin, µmol/L	≥17.1 vs <17.1	0.772	0.472–1.259	0.300
ALB, mg/L	≥35 vs <35	1.033	0.516–2.067	0.927
ALT, U/L	≥40 vs <40	0.737	0.474–1.147	0.176
AST, U/L	≥40 vs <40	1.359	0.875–2.111	0.172
PT, s	≥13 vs <13	1.519	0.980–2.353	0.061	1.149	0.705–1.871	0.578
INR	≥1 vs <1	1.208	0.715–2.041	0.479
Platelet count, 10^9 /L	≥225 vs <225	1.673	1.078–2.596	0.022	1.679	1.022–2.757	0.041
CTCs, n/5mL	>5 vs ≤5	3.324	1.994–5.539	0.000	2.467	1.430–4.258	0.001
AFP, µg/mL	≥200 vs <200	1.949	1.220–3.112	0.005	1.136	0.672–1.921	0.635
Tumor size, cm	≥5 vs <5	2.222	1.300–3.799	0.004	1.190	0.664–2.134	0.560
Multiple lesions	Yes vs no	1.671	1.056–2.645	0.028	1.392	0.805–2.406	0.237
Inflow blood occlusion	Yes vs no	1.162	0.701–1.926	0.561
Tumor capsule	Complete vs incomplete	0.593	0.357–0.984	0.043	0.589	0.336–1.030	0.063
Resection margin, cm	≥1 vs.<1	1.332	0.839–2.116	0.224
MVI	Positive vs negative	3.758	2.191–6.445	0.000	2.580	1.413–4.709	0.002
Histological grade	≥3 vs <3	0.830	0.535–1.289	0.406
Histological cirrhosis	Yes vs no	0.875	0.554–1.384	0.569
Satellite nodule	Yes vs no	1.902	1.155–3.132	0.012	1.196	0.673–2.126	0.542
Ki67	≥35% vs <35%	2.135	1.373–3.320	0.001	1.544	0.942–2.532	0.085
Postoperative adjuvant therapy	Yes vs no	1.192	0.770–1.847	0.431

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CI, confidence interval; CTCs, circulating tumor cell; HBV-DNA, hepatitis B virus DNA; HBsAg, hepatitis B surface antigen; HR, hazard ratio; INR, international normalized ratio; MVI, microvascular invasion; PT, prothrombin time.

Table 3 Subgroup Univariate and Multivariate Analyses of the Prognostic Factors Associated with the Early Recurrence of HCC

Characteristic	Comparison	Univariate			Multivariate
		HR	95% CI	P-value	HR	95% CI	P-value
Sex	Male vs female	1.090	0.538–2.207	0.811
Age, year	≥45 vs <45	0.671	0.409–1.101	0.115
BMI, kg/m^2	≥24 vs <24	0.447	0.264–0.756	0.003	0.602	0.344–1.053	0.075
Diabetes mellitus	Yes vs no	0.619	0.225–1.705	0.353
HBsAg	Positive vs negative	1.140	0.519–2.502	0.744
HBV-DNA, 10^2 IU/mL	≥5 vs <5	0.850	0.503–1.436	0.544
Child-Pugh class	A stage vs B stage	0.989	0.310–3.157	0.985
Total bilirubin, µmol/L	≥17.1 vs <17.1	0.723	0.405–1.291	0.273
ALB, mg/L	≥35 vs <35	0.936	0.462–1.896	0.853
ALT, U/L	≥40 vs <40	0.625	0.377–1.036	0.068
AST, U/L	≥40 vs <40	1.279	0.777–2.108	0.333
PT, s	≥13 vs <13	1.183	0.720–1.942	0.507
INR	≥1 vs <1	1.019	0.584–1.777	0.948
Platelet count, 10^9 /L	≥225 vs <225	2.474	1.451–4.219	0.001	1.976	1.091–3.543	0.024
CTCs, n/5mL	>5 vs ≤5	3.322	1.850–5.964	0.000	2.751	1.494–5.065	0.001
AFP, µg/mL	≥200 vs <200	1.681	1.006–2.811	0.047	0.840	0.471–1.500	0.556
Tumor size, cm	≥5 vs <5	2.662	1.352–5.2238	0.005	1.417	0.696–2.886	0.336
Multiple lesions	Yes vs no	1.608	0.944–2.737	0.080
Inflow blood occlusion	Yes vs no	1.176	0.649–2.130	0.594
Tumor capsule	Complete vs incomplete	0.572	0.319–1.024	0.060
Resection margin, cm	≥1 vs <1	1.676	0.997–2.817	0.052
MVI	Positive vs negative	3.563	2.010–6.315	0.000	2.074	1.087–3.959	0.027
Histological grade	≥3 vs <3	0.785	0.476–1.293	0.342
Histological cirrhosis	Yes vs no	0.514	0.262–1.012	0.054
Satellite nodule	Yes versus no	2.222	1.303–3.790	0.003	1.972	1.090–3.568	0.025
Ki67	≥35% vs <35%	1.801	1.096–2.958	0.020	1.546	0.933–2.562	0.091
Postoperative adjuvant therapy	Yes vs no	1.217	0.741–2.000	0.438

Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CI, confidence interval; CTCs, circulating tumor cell; HBV-DNA, hepatitis B virus DNA; HBsAg, hepatitis B surface antigen; HR, hazard ratio; INR, international normalized ratio; MVI, microvascular invasion; PT, prothrombin time.

Figure 4 ROC curves for preoperative (A) CTCs, (B) Platelet, and (C) CTCs-platelet to predict the early recurrence of HCC.

Figure 5 ROC curves of the subgroup patients for the preoperative (A) CTCs, (B) Platelet, and (C) CTCs-platelet to predict the early recurrence of HCC.