Onodera's Prognostic Nutritional Index is a novel and useful prognostic marker for gastrointestinal stromal tumors

Table 1 Clinicopathological features of 235 patients with primary gastrointestinal stromal tumors

Characteristic	n (%)
Gender
Male	118 (50.2)
Female	117 (49.8)
Age (yr, mean SD)	60.09 ± 10.12
≤ 60	110 (46.8)
> 60	125 (53.2)
Clinical manifestation
Abdominal discomfort or pain	104 (44.3)
Gastrointestinal bleeding	63 (26.8)
Obstruction	8 (3.4)
Perforation or rupture	2 (0.9)
Weight loss	7 (3.0)
Asymptomatic	51 (21.7)
Preoperative laboratory variables
Hemoglobin (g/L, mean SD)	122.69 ± 29.94
White blood cell (109 /L, mean SD)	6.52 ± 2.70
Neutrophil count (109 /L, mean SD)	4.40 ± 2.35
Lymphocyte count (109 /L, mean SD)	1.42 ± 0.53
Platelet count (109 /L, mean SD)	230.11 ± 100.76
Albumin (g/L, mean SD)	44.19 ± 6.66
NLR (mean SD)	3.80 ± 3.95
PLR (mean SD)	184.83 ± 109.06
OPNI (mean SD)	51.27 ± 7.12
Primary tumor site
Stomach	183 (77.9)
Small intestine	41 (17.4)
Colorectum	10 (4.3)
Intraperitoneally with unknown origin	1 (0.4)
Tumor size (cm, mean SD)	5.003 ± 3.5458
≤ 2.0	55 (23.4)
2.1-5.0	93 (39.6)
5.1-10.0	67 (28.5)
> 10.0	20 (8.5)
Predominant cell type
Spindle	206 (87.7)
Epithelioid	16 (6.8)
Mixed	13 (5.5)
Mitotic index (per 50 HPFs)
≤ 5	182 (77.4)
6-10	43 (18.3)
> 10	10 (4.3)
Necrosis
Yes	66 (28.1)
No	169 (71.9)
Tumor rupture
Yes	11 (4.7)
No	224 (95.3)
Risk classification
Very low risk	58 (24.7)
Low risk	77 (32.8)
Intermediate risk	41 (17.4)
High risk	59 (25.1)
CD117
(–)	4 (1.7)
(+)	169 (71.9)
(++)	18 (7.7)
(+++)	44 (18.7)
CD34
(–)	11 (4.7)
(+)	165 (70.2)
(++)	12 (5.1)
(+++)	47 (20.0)
DOG-1
(–)	3 (1.3)
(+)	211 (89.8)
(++)	12 (5.1)
(+++)	9 (3.8)
Ki-67 index (%, mean SD)	4.65 ± 6.37
Follow-up time (months, mean SD)	40.20 ± 20.18
Follow-up status
Relapse-free survival	215 (91.5)
Relapse	15 (6.4)
Metastasis	5 (2.1)

NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; OPNI: Onodera’s Prognostic Nutritional Index.

Table 2 Receiver operator characteristic analyses for neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Onodera’s Prognostic Nutritional Index, and ki-67 index

	NLR	PLR	OPNI	Ki-67 index
Cut-off point	4.34	220.76	51.30	2.5%
Sensitivity% (95%CI)	35.00 (25.73-45.19)	49.00 (38.86-59.20)	76.00 (66.43-83.98)	63.00 (52.76-72.44)
Specificity% (95%CI)	88.15 (81.47-93.07)	88.15 (81.47-93.07)	77.04 (69.02-83.83)	58.52 (49.73-66.93)
Youden Index	0.2315	0.3715	0.5304	0.2152
AUC (95%CI)	0.6308 (0.5584-0.7031)	0.6820 (0.6096-0.7545)	0.7999 (0.7420-0.8578)	0.6237 (0.5514-0.6960)
P value	0.0006	< 0.0001	< 0.0001	0.0012

NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; OPNI: Onodera’s Prognostic Nutritional Index; AUC: Area under the curve.

Table 3 Correlation analysis of tumor size and mitotic index with neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Onodera’s Prognostic Nutritional Index, and ki-67 index

	Tumor size		Mitotic index
	Pearson r	P value	Rs	P value
NLR	0.2082	0.0013	0.1021	0.1185
PLR	0.4098	< 0.0001	0.2045	0.0016
OPNI	-0.4955	< 0.0001	-3.048	< 0.0001
Ki-67 index	0.2727	< 0.0001	0.2551	< 0.0001

NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; OPNI: Onodera’s Prognostic Nutritional Index.

Table 4 Univariate analysis (Kaplan-Meier) of factors for recurrence-free survival in gastrointestinal stromal tumors

Factor	1-year RFS rate (95%CI)	2-year RFS rate (95%CI)	5-year RFS rate (95%CI)	Log-rank P value
Age (yr)				0.5441
≤ 60	99.09% (93.72-99.87)	96.92% (90.66-99.01)	91.20% (80.62-96.14)
> 60	99.20% (94.46-99.89)	96.35% (90.49-98.62)	82.93% (69.26-90.91)
Gender				0.2889
Male	98.31% (93.39-99.57)	95.19% (88.74-97.99)	84.07% (71.68-91.35)
Female	100%	98.03% (92.30-99.51)	84.96% (66.88-93.61)
GI bleeding				0.1877
Yes	98.41% (89.26-99.77)	98.41% (89.26-99.77)	82.02% (63.00-91.85)
No	99.42% (95.94-99.92)	95.84% (90.90-98.12)	89.37% (80.44-94.36)
Primary site				0.0093
Gastric	99.45% (96.18-99.92)	97.47% (93.30-99.04)	89.62% (79.32-94.94)
Non-gastric	98.08% (87.12-99.73)	93.75% (81.78-97.95)	79.12% (61.86-89.21)
Tumor size				0.0012
≤ 2.0 cm	100%	98.10% (87.12-99.73)	98.10% (87.12-99.73)
2.1-5.0 cm	100%	100%	94.90% (84.98-98.33)
5.1-10.0 cm	98.51% (89.87-99.79)	92.93% (82.17-97.30)	81.55% (65.45-90.65)
> 10.0 cm	95.00% (69.46-99.28)	90.00% (65.59-97.40)	56.00% (20.71-80.77)
Predominant cell type				0.7759
Spindle	99.51 % (96.60-99.93)	97.22 % (93.41-98.84)	88.47 % (79.83-93.55)
Epithelioid	93.75 % (63.22-99.10)	93.75 % (63.22-99.10)	84.38 % (49.30-96.00)
Mixed	100%	100%	76.39 % (30.91-94.01)
Mitotic index				< 0.0001
≤ 5 per 50 HPFs	100%	98.67% (94.75-99.67)	93.47% (85.43-97.15)
6-10 per 50 HPFs	97.67% (84.61-99.67)	91.93% (76.88-97.34)	77.13% (53.86-89.67)
>10 per 50 HPFs	100%	80.00% (40.86-94.59)	50.00% (18.35-75.32)
Necrosis				0.2676
Yes	98.48% (89.72-99.79)	98.48% (89.72-99.79)	83.69% (66.12-92.63)
No	100%	95.79% (90.79-98.10)	89.58% (81.22-94.34)
Tumor rupture				0.0695
Yes	100%	100%	63.49% (23.81-86.61)
No	99.11% (96.48-99.78)	96.43% (92.62-98.29)	88.40% (79.94-93.44)
Risk classification				0.0007
Very low risk	100%	98.18% (87.78-99.74)	98.18% (87.78-99.74)
Low risk	100%	100%	97.92% (86.11-99.70)
Intermediate risk	100%	100%	85.27% (59.66-95.20)
High risk	96.61% (87.11-99.14)	89.10% (77.27-94.97)	72.82% (56.21-83.98)
NLR				0.0224
< 4.34	99.46% (96.22-99.92)	98.89% (95.65-99.72)	88.76% (78.31-94.35)
≥ 4.34	98.00% (86.63-99.72)	88.68% (74.82-95.15)	80.29% (64.11-89.73)
PLR				0.0069
< 220.76	100%	99.39% (95.75-99.91)	91.24% (80.00-96.31)
≥ 220.76	96.92% (88.25-99.22)	89.64% (78.27-95.23)	77.17% (61.76-86.99)
OPNI				0.0002
≥ 51.30	100%	100%	98.41% (89.26-99.77)
< 51.30	98.13% (92.73-99.53)	92.83% (85.49-96.53)	76.22% (62.51-85.48)
Ki-67 index				0.0592
< 2.5%	100%	98.88% (92.29-99.84)	88.03% (68.96-95.72)
≥ 2.5%	98.29% (93.34-99.57)	94.34% (87.79-97.43)	84.39% (74.22-90.79)
Albumin				0.0589
< 38.95	99.86% (96.42-99.91)	98.79% (96.65-98.72)	89.74% (76.31-93.35)
≥ 38.95	99.01% (89.63-99.82)	90.68% (86.52-96.45)	87.23% (75.11-89.63)
Lymphocyte count				0.0524
< 0.975	99.46% (96.22-99.82)	96.89% (95.15-99.02)	88.76% (78.11-94.05)
≥ 0.975	98.70% (89.93-99.62)	90.68% (86.82-95.15)	87.29% (74.11-93.53)

GI: Gastrointestinal; RFS: Recurrence-free survival; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; OPNI: Onodera’s Prognostic Nutritional Index.

Table 5 Multivariate analysis [Cox regression analysis (Enter method)] for recurrence-free survival

Factor	Hazard ratio	95%CI	P value
Primary tumor site			0.0878
Gastric	1.000	-	-
Non-gastric	2.641	0.866-8.053	-
Tumor size (cm)			0.4749
≤ 2.0	1.000	-	-
2.1-5.0	1.318	0.006-292.720	0.9201
5.1-10.0	1.612	0.006-445.888	0.8678
> 10.0	4.765	0.015-1515.961	0.5953
Mitotic index (/50 HPFs)			0.03651
≤ 5	1.000	-	-
6-10	1.896	0.518-6.949	0.3341
>10	6.791	1.554-29.672	0.01091
Tumor rupture			0.5202
No	1.000	-	-
Yes	0.589	0.117-2.957	-
NIH risk classification			0.9763
Very low risk	1.000	-	-
Low risk	0.283	0.001-64.779	0.6491
Intermediate risk	0.282	0.001-91.515	0.6681
High risk	0.277	0.001-101.508	0.6702
NLR			0.7613
< 4.34	1.000	-	-
≥ 4.34	0.838	0.268-2.620	-
PLR			0.6958
< 220.76	1.000	-	-
≥ 220.76	1.259	0.397-3.995	-
OPNI			0.04141
≥ 51.30	1.000	-	-
< 51.30	5.852	1.072-31.964	-

¹With statistical significance. NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; OPNI: Onodera’s Prognostic Nutritional Index.