Decreased pretherapy serum apolipoprotein A-I is associated with extent of metastasis and poor prognosis of non-small-cell lung cancer

Figures & data

Table 1 Clinicopathologic factors in NSCLC patients and normal controls n (%)

Variable	NSCLC cases (n=325)	Normal controls (n=312)
Gender
Male	201 (61.8)	184 (59.0)
Female	124 (38.2)	128 (41.0)
Age (years)	60.14±9.73	59.16±11.54
Tobacco index
≤400	181 (55.7)	208 (66.7)
>400	144 (44.3)	104 (33.3)
BMI
≤24 kg/m^2	192 (59.1)	205 (65.7)
>24 kg/m^2	133 (40.9)	107 (34.3)
Histological subtype
Adenocarcinoma	176 (54.2)
Squamous cell carcinoma	114 (35.1)
Others	35 (10.8)
Greatest tumor diameter
≤3 cm	174 (53.5)
>3 cm	151 (46.5)
Clinical stage
I–II	99 (30.5)
III–IV	226 (69.5)
N stage
N0–2	248 (76.3)
N3	77 (23.7)
Distant metastases
≤2 sites	207 (63.7)
>2 sites	118 (36.3)
ECOG PS
0–1	276 (84.9)
2–4	49 (15.1)

Abbreviations: BMI, body mass index; NSCLC, non-small-cell lung cancer; PS, performance status.

Table 2 Relationship between ApoA-I and clinicopathologic factors in NSCLC patients

Variables	Cases (n)	ApoA-I (g/L)	P-value	ApoA-I (g/L)		P-value
		Mean ± SD		≤1.26	>1.26
Number of cases
Gender			0.323			0.212
Male	201	1.238±0.272		114	87
Female	124	1.210±0.270		79	45
Age (years)			0.364			0.113
≤60	165	1.213±0.267		105	60
>60	160	1.242±0.275		88	72
Tobacco index			0.249			0.212
≤400	181	1.239±0.280		102	79
>400	144	1.212±0.259		91	53
BMI			0.332			0.493
≤24 kg/m^2	192	1.211±0.281		117	75
>24 kg/m^2	133	1.250±0.255		76	57
CRP			0.046			0.027
≤10 mg/L	198	1.250±0.273		108	90
>10 mg/L	127	1.191±0.264		85	42
Albumin			0.040			0.004
≤35 g/L	98	1.182±0.289		70	28
>35 g/L	227	1.246±0.261		123	104
Histological subtype			0.186			0.190
Adenocarcinoma	176	1.202±0.261		111	65
Squamous cell carcinoma	114	1.265±0.294		60	54
Others	35	1.232±0.230		22	13
Greatest tumor diameter			0.089			0.308
≤3 cm	181	1.248±0.259		103	78
>3 cm	144	1.200±0.284		90	54
Clinical stage			0.004			0.025
I–II	89	1.300±0.267		44	45
III–IV	236	1.200±0.268		149	87
N stage			0.085			0.097
N0–2	222	1.250±0.267		125	97
N3	103	1.177±0.274		68	35
Tumor differentiation			0.202			0.079
Well and moderately differentiated	193	1.244±0.262		110	83
Poorly differentiated	132	1.201±0.284		88	44
ECOG PS			0.007			0.029
0–1	276	1.243±0.269		157	119
2–4	49	1.134±0.266		36	13
Extent of metastasis			<0.0001			<0.0001
≤2 sites	207	1.317±0.236		98	109
>2 sites	118	1.069±0.255		95	23
EGFR mutation			0.734			0.877
Mutation	86	1.261±0.226		47	39
Wild-type	122	1.244±0.283		68	54
Chemotherapy cycles			0.311			0.329
<4	106	1.200±0.294		67	39
≥4	219	1.240±0.258		126	93

Abbreviations: ApoA-I, apolipoprotein A-I; BMI, body mass index; CRP, C-reactive protein; NSCLC, non-small-cell lung cancer; PS, performance status.

Figure 1 ROC analysis for pretherapy serum ApoA-I to differentiate NSCLC patients from healthy controls. Area under ROC curve (AUC)=0.69, sensitivity=0.59, specificity=0.75, cutoff=1.26.

Abbreviations: ApoA-I, apolipoprotein A-I; NSCLC, non-small-cell lung cancer; ROC, receiver-operating characteristic.

Figure 2 Comparison of serum ApoA-I levels.

Notes: (A) Between NSCLC patients and normal controls; (B) in NSCLC patients with serum C-reactive protein level ≤10 and >10 mg/L; (C) in NSCLC patients with serum albumin level ≤35 and >35 g/L; (D) in NSCLC patients at different TNM stage; (E) in NSCLC patients with extent of distant metastasis ≤2 sites and >2 sites; (F) in NSCLC patients with different ECOG PS score.
Abbreviations: ApoA-I, apolipoprotein A-I; NSCLC, non-small-cell lung cancer; PS, performance status.

Table 3 Prognostic factors for overall survival in univariate and multivariate Cox analyses

Variable	Univariate analysis			Multivariate analysis
	HR	95% CI	P-value	HR	95% CI	P-value
Gender (male vs female)	1.083	0.863–1.358	0.493
Age (≤60 vs >60 years)	1.096	0.880–1.366	0.413
Tobacco index (≤400 vs >400)	0.937	0.750–1.172	0.570
BMI (≤24 vs >24)	0.976	0.780–1.221	0.829
CRP (≤10 vs >10 mg/L)	1.289	1.029–1.615	0.027	1.273	1.014–1.599	0.038
Albumin (≤35 vs >35 g/L)	1.368	1.077–1.738	0.010	1.242	0.970–1.590	0.086
Histological subtype	1.037	0.883–1.217	0.658
Adenocarcinoma (squamous cell carcinoma vs adenosquamous carcinoma vs others)
Greatest tumor diameter (≤3 vs >3 cm)	0.850	0.681–1.061	0.850
ApoA-I (≤1.26 vs >1.26 g/L)	0.609	0.485–0.765	<0.0001	0.761	0.594–0.975	0.030
Clinical stage (I–II vs III–IV)	1.320	1.029–1.692	0.029	1.206	0.936–1.554	0.148
N stage (N0–2 vs N3)	1.365	1.078–1.730	0.010	1.245	0.979–1.584	0.074
Tumor differentiation	1.146	0.913–1.439	0.241
(Well and moderately differentiated vs poorly differentiated)
ECOG PS (0–1 vs 2–4)	1.658	1.222–2.251	0.001	1.486	1.077–2.051	0.016
Extent of metastasis (≤2 sites vs >2 sites)	1.575	1.247–1.989	<0.0001	1.394	1.088–1.788	0.009
EGFR mutation (mutation vs wild-type)	1.266	0.952–1.683	0.104
Chemotherapy cycle (<4 vs ≥4)	1.246	0.986–1.575	0.066

Abbreviations: ApoA-I, apolipoprotein A-I; BMI, body mass index; CRP, C-reactive protein; PS, performance status.

Figure 3 Kaplan–Meier survival curves of 325 NSCLC patients.

Note: Overall survival rate of NSCLC patients with lower serum ApoA-I group was significantly shorter than those with higher serum ApoA-I group.
Abbreviations: ApoA-I, apolipoprotein A-I; cum, cumulative; NSCLC, non-small-cell lung cancer.