Prognostic scoring system using inflammation- and nutrition-related biomarkers to predict prognosis in stage I-III colorectal cancer patients

Table 1 Patient demographics and baseline characteristics, n (%)

Characteristic	Overall, n = 470	Training cohort, n = 282	Test cohort, n = 188	P value
Gender				0.283
Male	279 (59.4)	173 (61.3)	106 (56.4)
Female	191 (40.6)	109 (38.7)	82 (43.6)
Age, years				0.404
≤ 60	209 (44.5)	121 (42.9)	88 (46.8)
> 60	261 (55.5)	161 (57.1)	100 (53.2)
BMI, kg/m2				0.762
≤ 24	216 (46.0)	128 (45.4)	88 (46.8)
> 24	254 (54.0)	154 (54.6)	100 (53.2)
Smoking				0.419
Yes	150 (31.9)	94 (33.3)	56 (29.8)
No	320 (68.1)	188 (66.7)	132 (70.2)
Alcohol				0.113
Yes	89 (18.9)	60 (21.3)	29 (15.4)
No	381 (81.1)	222 (78.7)	159 (84.6)
CEA				0.639
Normal	299 (63.6)	177 (62.8)	122 (64.9)
High	171 (36.4)	105 (37.2)	66 (35.1)
Gross appearance				0.741
Bulge	139 (29.6)	85 (30.1)	54 (28.7)
Infiltration or ulcer	331 (70.4)	197 (69.9)	134 (71.3)
Histological type				0.418
Adenocarcinoma	437 (93.0)	260 (92.2)	177 (94.1)
Mucinous adenocarcinoma or signet ring cell cancer	33 (7.0)	22 (7.8)	11 (5.9)
Nerve invasion				0.883
Negative	386 (82.1)	231 (81.9)	155 (82.4)
Positive	84 (17.9)	51 (18.1)	33 (17.6)
Intravascular tumor emboli				0.846
Negative	383 (81.5)	229 (81.2)	154 (81.9)
Positive	87 (18.5)	53 (18.8)	34 (18.1)
T stage				0.221
T1-T2	104 (22.1)	57 (20.2)	47 (25.0)
T3-T4	366 (77.9)	225 (79.8)	141 (75.0)
N stage				0.506
N0-N1	394 (83.8)	239 (84.8)	155 (82.4)
N2-N3	76 (16.2)	43 (15.2)	33 (17.6)
TNM stage				0.298
I-II	284 (60.4)	165 (58.5)	119 (63.3)
III	186 (39.6)	117 (41.5)	69 (36.7)
Differentiated degree				0.176
Well/moderate	73 (15.5)	49 (17.4)	24 (12.8)
Poor/undifferentiated	397 (84.5)	233 (82.6)	164 (87.2)
NLR median (IQR)	2.00 (1.50, 2.69)	2.03 (1.51, 2.82)	1.96 (1.49, 2.56)	0.333
MLR median (IQR)	0.24 (0.19, 0.33)	0.25 (0.20, 0.33)	0.24 (0.19, 0.31)	0.342
PLR median (IQR)	131.32 (101.58, 173.39)	130 (101, 175)	132 (103, 173)	0.905
ALI median (IQR)	486.92 (371.72, 673.36)	486 (366, 674)	492 (378, 669)	0.499
PIV median (IQR)	210.31 (135.42, 334.68)	220 (137, 337)	204 (130, 333)	0.403
SII median (IQR)	473.60 (330.39, 703.21)	474 (333, 712)	472 (326, 680)	0.732
SIRI median (IQR)	0.86 (0.59, 1.34)	0.88 (0.61, 1.40)	0.81 (0.57, 1.25)	0.171
PNI median (IQR)	50.20 (46.86, 52.94)	49.9 (46.8, 53.0)	50.4 (47.0, 52.8)	0.486
GNRI median (IQR)	106.50 (100.81, 112.72)	106 (100, 113)	107 (101, 113)	0.630
AGR median (IQR)	1.49 (1.33, 1.68)	1.49 (1.32, 1.72)	1.49 (1.34, 1.65)	0.975

IQR: Interquartile range; BMI: Body mass index; CEA: Carcinoembryonic antigen; NLR: Neutrophil to lymphocyte ratio; MLR: Monocyte-to-lymphocyte ratio; PLR: Platelet to lymphocyte ratio; ALI: Advanced lung cancer inflammation index; PIV: Pan-immune-inflammation; SII: Systemic immune inflammation index; SIRI: Systemic Inflammation Response Index; PNI: Prognostic nutritional index; GNRI: Geriatric nutrition risk index; AGR: Albumin to globulin ratio.

Table 2 Univariate Cox analyses for overall survival of inflammation-related and nutrition-related biomarkers in the training set

Variable	Cutoff value	Categories	HR	95%CI	P value
NLR	2.07	High (≥ 2.07) vs low (< 2.07)	3.07	1.86, 5.05	< 0.001
MLR	0.28	High (≥ 0.28) vs low (< 0.28)	4.09	2.52, 6.62	< 0.001
PLR	166.66	High (≥ 166.66) vs low (< 166.66)	2.74	1.74, 4.34	< 0.001
PIV	348.45	High (≥ 348.45) vs low (< 348.45)	7.23	4.52, 11.57	< 0.001
SII	576.92	High (≥ 576.92) vs low (< 576.92)	3.40	2.12, 5.44	< 0.001
SIRI	14.15	High (≥ 14.15) vs low (< 14.15)	6.45	4.02, 10.34	< 0.001
PNI	47.05	High (≥ 47.05) vs low (< 47.05)	0.50	0.32, 0.79	0.003
GNRI	103.95	High (≥ 103.95) vs low (< 103.95)	0.40	0.25, 0.63	< 0.001
AGR	1.40	High (≥ 1.40) vs low (< 1.40)	0.23	0.14, 0.38	< 0.001
ALI	367.75	High (≥ 367.75) vs low (< 367.75)	0.27	0.17, 0.42	< 0.001

NLR: Neutrophil to lymphocyte ratio; MLR: Monocyte-to-lymphocyte ratio; PLR: Platelet to lymphocyte ratio; ALI: Advanced lung cancer inflammation index; PIV: Pan-immune-inflammation; SII: Systemic immune inflammation index; SIRI: Systemic Inflammation Response Index; PNI: Prognostic nutritional index; GNRI: Geriatric nutrition risk index; AGR: Albumin to globulin ratio; HR: Hazard ratio.

Table 3 Univariate and multivariate Cox analyses of baseline characteristics and risk score on overall survival in colorectal cancer patients

Characteristics	Univariate analysis HR (95%CI)	P value	Multivariate analysis HR (95%CI)	P value
Age, years
≤ 60	Reference
> 60	0.98 (0.68-1.41)	0.921
Gender
Male	Reference
Female	1.30 (0.90-1.87)	0.163
BMI, kg/m2
≤ 24	Reference
> 24	1.12 (0.78-1.60)	0.550
Smoking
Yes	Reference
No	1.50 (1.00-2.26)	0.051
Alcohol
Yes	Reference
No	1.20 (0.75-1.92)	0.453
Gross appearance
Bulge	Reference		Reference
Infiltration or ulcer	1.58 (1.03-2.42)	0.037	1.06 (0.67-1.68)	0.812
Histological type
Adenocarcinoma	Reference
Mucinous adenocarcinoma or signet ring cell cancer	1.56 (0.86-2.84)	0.141
T stage
T1-T2	Reference		Reference
T3-T4	4.12 (2.09-8.12)	< 0.001	1.66 (0.80-3.43)	0.175
N stage
N0-N1	Reference		Reference
N2-N3	2.40 (1.61-3.58)	< 0.001	1.61 (1.00-2.59)	0.052
TNM stage
I-II	Reference		Reference
III	2.09 (1.46-2.98)	< 0.001	1.26 (0.82-1.93)	0.285
Differentiated degree
Poor/undifferentiated	Reference		Reference
Well/moderate	2.64 (1.77-3.92)	< 0.001	2.04 (1.33-3.13)	0.001
Nerve invasion
Negative	Reference		Reference
Positive	2.48 (1.69-3.66)	< 0.001	1.66 (1.08-2.55)	0.022
Intravascular tumor emboli
Negative	Reference		Reference
Positive	1.56 (1.03-2.37)	0.036	1.05 (0.67-1.65)	0.837
CEA
Normal	Reference		Reference
High	1.69 (1.19-2.42)	0.004	1.25 (0.85-1.82)	0.255
RS
< 266.24	Reference		Reference
≥ 266.24	6.86 (4.77-9.86)	< 0.001	6.62 (4.56-9.62)	< 0.001

BMI: Body mass index; CEA: Carcinoembryonic antigen; RS: Risk factor; HR: Hazard ratio.