Derived neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio may be better biomarkers for predicting overall survival of patients with advanced gastric cancer

Figures & data

Table 1 Characteristic of GC patients

Variable	N (%)
Sex
Female	523 (26.3)
Male	1,467 (73.7)
Age (year)
≤62	1,232 (61.9)
>62	758 (38.1)
Tumor depth
T1	124 (6.2)
T2	187 (9.4)
T3	512 (25.7)
T4	1,167 (58.7)
Lymph nodes
N0	460 (23.1)
N1	343 (17.2)
N2	447 (22.5)
N3	740 (37.2)
Metastasis
M0	1,781 (89.5)
M1	209 (10.5)
AJCC stage
I	162 (8.1)
II	476 (23.9)
III	1,143 (57.5)
IV	209 (10.5)
Radicality
R0	1,468 (73.8)
R1 or R2	522 (26.2)
Tumor size (cm)
≤6	1,290 (64.8)
>6	700 (35.2)
Location
Upper	273 (13.7)
Middle	371 (18.6)
Low	1,160 (58.3)
Whole	186 (9.4)
MLNRa
≤31.5%	1,155 (58.0)
>31.5%	835 (42.0)
Differentiationb
Differentiated	322 (16.2)
Undifferentiated	1,668 (83.8)
Ascites
No	1,912 (96.1)
Yes	78 (3.9)
CA19–9 (U/mL)
≤37	1,556 (78.2)
>37	434 (21.8)
CEA (ng/mL)
≤5	1,527 (76.7)
>5	463 (23.3)
Hb (g/L)
≤130	1,014 (51.0)
>130	976 (49.0)
Tobacco
Yes	985 (49.5)
No	1,005 (50.5)
dNLR
≤1.73	1,206 (60.6)
>1.73	784 (39.4)
MLR
≤0.22	917 (46.1)
>0.22	1,073 (53.9)
NLR
≤2.10	1,018 (51.2)
>2.10	972 (48.8)
PLR
≤139.12	908 (45.6)
>139.12	1,082 (54.4)
PNI
≤51.07	960 (48.2)
>51.07	1,030 (51.8)

Notes:

a The average point of MLNR was 31.5%.

b Grades1 and 2 were differentiated, and grades 3 and 4 were undifferentiated.

Abbreviations: AJCC, American Joint Committee on Cancer; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; dNLR, derived neutrophil to lymphocyte ratio; GC, gastric cancer; Hb, hemoglobin; MLNR, Metastatic lymph nodes ratio; MLR, monocyte to lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; PNI, prognostic nutritional index.

Figure 1 Optimal cut-off points for NLR, dNLR, MLR, PLR, and PNI were applied with ROC curves.

Abbreviations: dNLR, derived neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; PNI, prognostic nutritional index; ROC, receiver operating characteristics.

Table 2 The optimal cut-off point for overall survival

Variables	AUC	Cut-off point	P-value
NLR	0.555	2.10	<0.001
dNLR	0.551	1.73	<0.001
MLR	0.554	0.22	<0.001
PLR	0.576	139.12	<0.001
PNI	0.395	–	<0.001

Note: ‘–’ indicates no appropriate cut-off point.

Abbreviations: AUC, area under the curve; NLR, neutrophil to lymphocyte ratio; dNLR, derived neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; PLR, platelet to lymphocyte ratio; PNI, prognostic nutritional index.

Table 3 Relationship between clinicopathological characteristics and NLR, dNLR, MLR, PLR, and PNI

Factors	NLR			dNLR			MLR			PLR			PNI
	NLR ≤2.10	χ^2	P-value	dNLR≤1.73	χ^2	P-value	MLR≤0.22	χ^2	P-value	PLR≤139.12	χ^2	P-value	PNI ≤51.07	χ^2	P-value
Sex			0.075			0.143			0.001			<0.001			0.943
Male	733	3.163		875	2.143		643	11.368		706	14.032		707	0.005
Female	285			331			274			202			253
Age (year)			0.01			0.043			<0.001			0.066			0.389
≤62	658	6.572		768	4.076		610	15.338		582	3.388		585	0.743
>62	360			438			307			326			375
Tumor depth			<0.001			0.051			0.001			<0.001			<0.001
T1	79	22.075		83	7.753		75	16.178		84	49.662		36	44.861
T2	118			127			90			112			60
T3	254			309			249			233			265
T4	567			687			503			479			599
Lymph nodes			<0.001			0.025			0.003			<0.001			<0.001
N0	251	21.328		286	9.339		234	14.14		243	25.644		185	30.762
N1	188			221			159			169			159
N2	250			282			221			209			203
N3	329			417			303			287			413
Metastasis			<0.001			0.001			<0.001			<0.001			<0.001
M0	944	23.181		1,101	10.505		855	25.326		837	12.791		831	16.998
M1	74			105			62			71			129
AJCC stages			<0.001			0.003			<0.001			<0.001			<0.001
I	100	31.239		105	13.677		91	32.253		103	43.485		47	46.379
II	263			307			238			246			206
III	581			689			526			488			578
IV	74			105			62			71			129
Radicality			<0.001			<0.001			<0.001			<0.001			<0.001
R0	815	42.615		943	30.955		728	27.764		743	56.056		638	51.226
R1 or R2	203			263			189			165			322
Tumor size (cm)			<0.001			<0.001			<0.001			<0.001			<0.001
≤6	736	51.064		840	31.287		640	18.413		680	74.203		521	90.59
>6	282			366			277			228			439
Location			0.223			0.644			0.14
Upper	140	4.38		170	1.667		108	5.479		128	4.232	0.237	119	4.223	0.238
Middle	172			215			175			158			187
Low	610			705			548			546			557
Whole	96			116			86			76			97
MLNR			<0.001			<0.001			<0.001			<0.001			<0.001
≤31.5%	652	30.88		744	16.758		579	18.167		588	30.943		502	25.167
>31.5%	366			462			338			320			458
Differentation			0.876			0.31			0.68			0.992			0.351
Differentiated	166	0.024		187	1.029		145	0.17		147	<0.001		163	0.871
Undifferentiated	852			1,019			772			761			797
Ascites			<0.001			<0.001			0.038			<0.001			<0.001
No	996	17.114		1,176	16.669		890	4.295		892	20.641		904	18.037
Yes	22			30			27			16			56
CA19–9 (µ/mL)			0.005			0.045			0.017			<0.001			0.17
≤37	822	7.982		961	4.007		739	5.735		742	12.183		738	1.884
>37	196			245			178			166			222
CEA (ng/mL)			<0.001			0.005			0.017			0.007			0.216
≤5	824	20.685		951	7.721		726	5.66		722	7.238		725	1.528
>5	194			255			191			186			235
Hb (g/L)			<0.001			<0.001			<0.001			<0.001			<0.001
≤130	435	56.404		545	40.697		399	25.326		280	270.452		644	193.062
>130	583			661			518			628			316
Tobacco			0.537			0.201			0.992			0.001			0.665
Yes	497	0.381		583	1.636		454	<0.001		488	12.05		480	0.187
No	521			623			463			420			480

Abbreviations: AJCC, American Joint Committee on Cancer; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; dNLR, derived neutrophil to lymphocyte ratio; Hb, hemoglobin; MLNR, metastatic lymph node ratio; MLR, monocyte to lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; PNI, prognostic nutritional index.

Figure 2 Kaplan–Meier curves for overall survival according to NLR, dNLR, MLR, PLR, and PNI.

Abbreviations: dNLR, derived neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; PNI, prognostic nutritional index.

Table 4 Univariate and multivariate analysis of factors for overall survival

Factors	Univariate	Multivariate
	P-value	HR (95% CI)	P-value
Sex	0.836
Age (year)	<0.001	1.196 (1.071–1.336)	0.002
Tumor depth	<0.001	1.181 (1.066–1.308)	0.001
Lymph nodes	<0.001	1.215 (1.105–1.336)	<0.001
Distant metastasis	<0.001	0.667 (0.508–0.875)	0.004
AJCC stage	<0.001	2.087 (1.698–2.566)	<0.001
Radicality	<0.001	2.140 (1.860–2.463)	<0.001
Tumor size (cm)	<0.001	1.311 (1.164–1.476)	<0.001
Tumor location	<0.001	0.958 (0.899–1.020)	0.180
MLNR	<0.001	1.295 (1.104–1.519)	0.001
Differentiation	<0.001	1.188 (1.018–1.385)	0.029
Ascites	<0.001	1.241 (0.965–1.595)	0.092
CA19–9 (µ/mL)	<0.001	1.218 (1.076–1.378)	0.002
CEA (ng/mL)	<0.001	1.182 (1.045–1.336)	0.008
Hb (g/L)	<0.001	1.004 (0.892–1.130)	0.944
Tobacco	0.376
dNLR	<0.001	1.202 (1.007–1.435)	0.042
MLR	<0.001	1.156 (1.023–1.305)	0.020
NLR	<0.001	0.861 (0.714–1.039)	0.119
PLR	<0.001	0.933 (0.820–1.062)	0.291
PNI	<0.001	0.951 (0.842–1.075)	0.423

Abbreviations: AJCC, American Joint Committee on Cancer; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; dNLR, derived neutrophil to lymphocyte ratio; Hb, hemoglobin; HR, hazard ratio; MLNR, metastatic lymph node ratio. MLR, monocyte to lymphocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; PNI, prognostic nutritional index.

Figure 3 Kaplan–Meier curves for overall survival according to scores of dNLR and MLR.

Abbreviations: dNLR, derived neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio.

Figure 4 Overall survival stratified by TNM stage of dNLR, MLR, and their combination score. A, D, G, and J were stages I, II, III, and IV of dNLR, respectively; B, E, H and K were stages I, II, III, and IV of MLR, respectively; C, F, I, and L were stages I, II, III, and IV of their combination scores.

Abbreviations: dNLR, derived neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio.