Prognostic Significance of Platelet-to-Lymphocyte Ratio (PLR) in Extrahepatic Metastasis of Hepatocellular Carcinoma After Curative Resection

Figures & data

Figure 1 The flow chart of selected patients.

Abbreviation: HCC, hepatocellular carcinoma.

Table 1 The Optimal Cut-Off Value for NLR, PLR, LMR, PNI, and NγLR Calculated by the ROC Curve

Variables	Cut-Off Value	AUC	95% CI	Sensitivity	Specificity	p-value
NLR	2.65	0.573	0.527–0.619	0.333	0.789	0.002
PLR	107.67	0.592	0.547–0.637	0.572	0.621	<0.001
LMR	5.47	0.554	0.509–0.599	0.480	0.650	0.019
PNI	51.23	0.552	0.509–0.595	0.398	0.706	0.024
NγLR	134.52	0.620	0.577–0.663	0.578	0.619	<0.001
PNLR	335.03	0.594	0.548–0.639	0.522	0.636	<0.001

Abbreviations: AUC, area under the ROC curve; CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; PNI, prognostic nutritional index; NγLR, (neutrophil times γ-GT)-to-lymphocyte ratio.

Table 2 Comparison of Clinicopathological Characteristics Between Metastasis and Non-Metastasis

Variables	Non-Metastasis Group (n=1186)	Metastasis Group (n=180)	p-value
Age, years, Median [IQR]	52.0 [45.0, 60.0]	50.0 [43.0, 60.0]	0.334
Gender
Female	170 (14.3%)	22 (12.2%)	0.519
Male	1016 (85.7%)	158 (87.8%)
BCLC
Stage 0	60 (5.1%)	4 (2.2%)	0.002
Stage A	955 (80.5%)	133 (73.9%)
Stage B	171 (14.4%)	43 (23.9%)
TNM stage (8th)
IA	68 (5.7%)	4 (2.2%)	<0.001
IB	713 (60.1%)	94 (52.2%)
II	305 (25.7%)	51 (28.3%)
IIIA	100 (8.4%)	31 (17.2%)
HBsAg
Negative	116 (9.8%)	23 (12.8%)	0.268
Positive	1070 (90.2%)	157 (87.2%)
HBV-DNA
<1000IU/mL	663 (55.9%)	103 (57.2%)	0.801
≥1000IU/mL	523 (44.1%)	77 (42.8%)
AFP, ng/mL, Median [IQR]	42.6 [5.40, 692]	87.1 [8.33, 1210]	0.001
WBC, 10^9/L, Mean (SD)	5.25 (1.54)	5.55 (1.79)	0.036
RBC, 10^12/L, Mean (SD)	4.61 (0.522)	4.69 (0.620)	0.127
HB, g/L, Mean (SD)	142 (16.0)	142 (15.9)	0.912
PLT, 10^9/L, Mean (SD)	160 (68.5)	175 (70.7)	0.008
ALB, g/L, Mean (SD)	42.1 (3.70)	41.6 (3.39)	0.069
TBIL, μmol/L, Median [IQR]	13.2 [10.5, 16.6]	12.6 [10.2, 16.5]	0.420
GGT, U/L, Median [IQR]	54.0 [32.0, 97.0]	76.0 [42.0, 124]	0.005
Surgical margin width
<1cm	962 (81.1%)	150 (83.3%)	0.541
≥1cm	224 (18.9%)	30 (16.7%)
Blood transfusion
NO	1106 (93.3%)	156 (86.7%)	0.003
YES	80 (6.7%)	24 (13.3%)
Operative bleeding loss
<800mL	1113 (93.8%)	158 (87.8%)	0.005
≥800mL	73 (6.2%)	22 (12.2%)
Tumor diameter
<5cm	662 (55.8%)	58 (32.2%)	<0.001
≥5cm	524 (44.2%)	122 (67.8%)
Tumor number
Single	984 (83.0%)	133 (73.9%)	0.005
Multiple	202 (17.0%)	47 (26.1%)
Microvascular invasion
NO	888 (74.9%)	124 (68.9%)	0.106
YES	298 (25.1%)	56 (31.1%)
Edmondson grade
I–II	155 (13.1%)	12 (6.7%)	0.020
III–IV	1031 (86.9%)	168 (93.3%)
Tumor capsule
NO	204 (17.2%)	37 (20.6%)	0.320
YES	982 (82.8%)	143 (79.4%)
Satellite nodules
NO	778 (65.6%)	107 (59.4%)	0.127
YES	408 (34.4%)	73 (40.6%)
Liver cirrhosis
NO	388 (32.7%)	73 (40.6%)	0.047
YES	798 (67.3%)	107 (59.4%)
NLR
<2.65	936 (78.9%)	120 (66.7%)	<0.001
≥2.65	250 (21.1%)	60 (33.3%)
PLR
<107.67	736 (62.1%)	77 (42.8%)	<0.001
≥107.67	450 (37.9%)	103 (57.2%)
LMR
<5.47	617 (52.0%)	117 (65.0%)	0.002
≥5.47	569 (48.0%)	63 (35.0%)
NγLR
<134.52	734 (61.9%)	76 (42.2%)	<0.001
≥134.52	452 (38.1%)	104 (57.8%)
PNLR
<335.03	754 (63.6%)	86 (47.8%)	<0.001
≥335.03	432 (36.4%)	94 (52.2%)
PNI
<51.23	714 (60.2%)	127 (70.6%)	0.010
≥51.23	472 (39.8%)	53 (29.4%)

Abbreviations: BCLC, Barcelona Clinic Liver Cancer; TNM, tumor-node-metastases; HBsAg, hepatitis B surface antigen; HBV-DNA, hepatitis B virus deoxyribonucleic acid; AFP, alpha-fetoprotein; WBC, white blood cell; RBC, red blood cell; HB, hemoglobin; PLT, platelet count; ALB, albumin; TBIL, total bilirubin; GGT, gamma-glutamyltransferase; SD, standard deviation; IQR, interquartile range; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; PNI, prognostic nutritional index; NγLR, (neutrophil times γ-GT)-to-lymphocyte ratio.

Table 3 Univariate and Multivariate Cox Regression for Extrahepatic Metastasis in HCC Patients After Radical Resection

Variables	Univariate			Multivariate
	HR	95% CI	p-value	HR	95% CI	p-value
Age: ≥60year vs <60year	1.012	0.727–1.408	0.946
Gender: male vs female	1.208	0.773–1.887	0.407
HBsAg: positive vs negative	0.761	0.491–1.178	0.221
HBV-DNA: ≥1000IU/mL vs<1000IU/mL	1.009	0.751–1.356	0.953
AFP, ng/mL	1.001	1.000–1.001	<0.001	1.001	1.000–1.001	0.004
RBC, 10^12/L	1.265	0.962–1.664	0.093
HB, g/L	1.000	0.991–1.009	0.991
TBIL, μmol/L	0.989	0.961–1.018	0.451
Surgical margin width: ≥1cm vs <1cm	0.817	0.552–1.209	0.311
Blood transfusion: yes vs no	2.269	1.475–3.488	<0.001	1.157	0.577–2.320	0.681
Operative bleeding loss: ≥800mL vs <800mL	2.397	1.534–3.748	<0.001	1.220	0.591–2.518	0.591
Tumor diameter: ≥5cm vs <5cm	2.843	2.078–3.888	<0.001	1.926	1.355–2.737	<0.001
Tumor number: multiple vs single	1.882	1.349–2.626	<0.001	1.611	1.021–2.542	0.040
Microvascular invasion: yes vs no	1.554	1.133–2.132	0.006	1.308	0.930–1.841	0.123
Edmondson grade: III–IV vs I–II	2.258	1.257–4.057	0.006	1.351	0.735–2.482	0.332
Tumor capsule: yes vs no	0.736	0.513–1.057	0.097
Satellite nodules: yes vs no	1.435	1.065–1.933	0.017	0.994	0.650–1.520	0.978
Liver cirrhosis: yes vs no	0.747	0.555–1.006	0.054
NLR: ≥2.65 vs <2.65	1.881	1.380–2.565	<0.001	0.990	0.665–1.473	0.959
PLR: ≥107.67 vs <107.67	2.190	1.630–2.943	<0.001	1.488	1.015–2.184	0.042
LMR: ≥5.47 vs <5.47	0.562	0.414–0.764	<0.001	0.831	0.588–1.174	0.294
NγLR: ≥134.52 vs <134.52	2.351	1.748–3.161	<0.001	1.397	0.987–1.978	0.059
PNLR: ≥335.03 vs <335.03	1.875	1.400–2.513	<0.001	0.894	0.591–1.354	0.598
PNI: ≥51.23 vs <51.23	0.617	0.448–0.851	0.003	0.784	0.556–1.105	0.165

Abbreviations: HR, hazard ratio; CI, confidence interval; HBsAg, hepatitis B surface antigen; HBV-DNA, hepatitis B Virus deoxyribonucleic acid; AFP, alpha-fetoprotein; RBC, red blood cell; HB, hemoglobin; TBIL, total bilirubin; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio; PNI, prognostic nutritional index; NγLR, (neutrophil times γ-GT)-to-lymphocyte ratio.

Figure 2 Comparison of metastasis rate between high and low PLR groups.

Abbreviation: PLR, platelet-to-lymphocyte ratio.

Figure 3 Subgroup analysis of metastasis rate between high and low PLR groups. (A) Metastasis rate in the BCLC stage 0/A patients; (B) metastasis rate in the BCLC stage B patients.

Abbreviations: PLR, platelet-to-lymphocyte ratio; BCLC, Barcelona Clinic Liver Cancer.

Figure 4 Subgroup analysis of metastasis rate between high and low PLR groups. (A) Metastasis rate in the normal AFP level group (<20ng/mL); (B) metastasis rate in the abnormal AFP level group (≥20ng/mL and <400ng/mL); (C) metastasis rate in the higher AFP level group (≥400ng/mL).

Abbreviations: PLR, platelet-to-lymphocyte ratio; AFP, alpha-fetoprotein.

Figure 5 Subgroup analysis of metastasis rate between high and low PLR groups. (A) Metastasis rate in the non-cirrhosis group; (B) metastasis rate in the cirrhosis group.

Abbreviation: PLR, platelet-to-lymphocyte ratio.

Figure 6 Subgroup analysis of metastasis rate between high and low PLR groups. (A) Metastasis rate in the HBsAg negative group; (B) metastasis rate in the HBsAg positive group.

Abbreviations: PLR, platelet-to-lymphocyte ratio; HBsAg, hepatitis B surface antigen.