Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy

Table 1 The basic clinical information of enrolled non-small cell lung cancer patients

Variables	PD/SD, n = 62	CR/PR, n = 97	t/χ2/Z	P value
Age group			0.832	0.362
< 60 yr	34 (54.8)	46 (47.4)
≥ 60 yr	28 (45.2)	51 (52.6)
Sex			0.313	0.576
Female	11 (17.7)	14 (14.4)
Male	51 (82.3)	83 (85.6)
BMI	22 (16.02, 27.7)	22.39 (16.33, 29.69)	0.242	0.842
Histologic subtypes			2.586	0.108
Squamous carcinoma	33 (53.2)	64 (66.0)
Adenocarcinoma	29 (46.8)	33 (34.0)
Smoking index			1.451	0.237
< 400	20 (32.3)	23 (23.7)
≥ 400	42 (67.7)	74 (76.3)
PS scoring			0.477	0.788
0	10 (16.1)	19 (19.6)
1	50 (80.6)	76 (78.4)
2	2 (3.2)	2 (2.1)
T stage			1.685	0.641
1	2 (3.2)	8 (8.2)
2	18 (29.1)	25 (25.8)
3	11 (17.7)	17 (17.5)
4	31 (50)	47 (48.5)
N stage			0.319	0.956
0	2 (3.2)	4 (4.1)
1	12 (19.4)	21 (21.6)
2	26 (41.9)	41 (42.3)
3	22 (35.5)	31 (32.0)
M stage			1.994	0.425
0	13 (21.0)	18 (18.6)
1	49 (89.0)	45 (81.4)

Data are n (%). BMI: Body mass index; CR: Complete response; PD: Progressive disease; PR: Partial response; PS: Performance status; SD: Stable disease.

Table 2 Potential clinical factors correlated with chemoimmunotherapy efficacy in non-small cell lung cancer patients

Factors	PD/SD, n = 62	CR/PR, n = 97	t/χ2/Z	P value
IL-6 in pg/mL	16.38 (0.14, 92.85)	17.93 (0.05, 219.79)	0.616	0.538
IL-8 in pg/mL	146.29 (19.87, 1038.52)	112.19 (15.76, 915.15)	1.986	0.047
PD-L1			2.413	0.035
< 1%	20 (32.3)	35 (36.1)
1%-49%	38 (61.3)	43 (44.3)
> 50%	4 (6.4)	19 (19.6)
NETs in pg/mL	740.63 (28.05, 3128.41)	467.54 (11.36, 2036.62)	2.564	0.011
Neutrophil percent	5.88 (1.93, 10.85)	5.09 (1.35, 13.5)	2.078	0.058
CD3 cell percent	63.03 (28.22, 86.55)	64.30 (29.63, 85.35)	0.533	0.594
CD4 cell percent	35.64 (17.56, 53.86)	37.88 (16.13, 62.02)	1.199	0.231
CD8 cell percent	25.07 (10.25, 64.67)	24.13 (10.28, 46.54)	0.215	0.829
B cell percent	10.88 (0.77, 36.50)	8.96 (0.98, 23.31)	1.831	0.067
NK cell percent	23.89 (5.90, 65.47)	24.79 (6.76, 53.68)	0.496	0.622
NLR	4.14 (2.43, 5.81)	3.13 (2.3, 4.2)	2.551	0.011
NLR grouping			6.947	0.008
≤ 4	32 (51.6)	70 (72.2)
> 4	30 (48.4)	27 (27.8)
Lymphocyte percent	1.53 (0.38, 3.04)	1.56 (0.67, 3.32)	0.457	0.647
Hepatic metastases			1.428	0.232
No	47 (75.8)	81 (83.5)
Yes	15 (24.2)	16 (16.5)
Bone metastasis			2.109	0.146
No	49 (79.0)	85 (87.6)
Yes	13 (21.0)	12 (12.4)
Metastatic sites			1.067	0.302
< 3	42 (67.7)	73 (75.3)
≥ 3	20 (32.3)	24 (24.7)

Data are n (%). CR: Complete response; IL: Interleukin; NETs: Neutrophil extracellular traps; NK: Natural killer; NLR: Neutrophil to lymphocyte ratio; PD: Progressive disease; PR: Partial response; SD: Stable disease.

Table 3 Univariate analysis of chemoimmunotherapy efficacy in non-small cell lung cancer patients

Variables	Univariate analysis
	HR	OR (95%CI)	P value
Age	1.004	0.956-1.061	0.798
Sex	1.047	0.305-2.734	0.871
Histologic subtypes	2.033	0.835-4.817	0.119
IL-6	1.005	0.990-1.023	0.463
IL-8	1.000	0.997-1.002	0.762
NETs	0.999	0.998-1.000	0.006
PS score	0.494	0.193-1.267	0.142
T stage	0.858	0.600-1.352	0.614
N stage	0.863	0.576-1.504	0.769
M stage	0.326	0.276-1.626	0.376
PD-L1 expression	1.029	1.010-1.051	0.004
CD3 percentage	0.985	0.919-1.079	0.769
CD4 percentage	1.068	0.989-1.156	0.094
CD8 percentage	1.008	0.941-1.079	0.827
NK percentage	1.025	0.969-1.093	0.354
B cell percentage	0.933	0.860-1.025	0.162
NLR	1.135	0.739-1.739	0.565
PMN percentage	0.784	0.544-1.141	0.206
Lymphocyte percentage	0.811	0.457-5.365	0.476

CI: Confidence interval; HR: Hazard ratio; IL: Interleukin; NETs: Neutrophil extracellular traps; NK: Natural killer; NLR: Neutrophil-to-lymphocyte ratio; OR: Odds ratio; PMN: Polymorphonuclear neutrophil; PS: Performance status.