Prognostic Implication of Metabolic Syndrome in Patients with Nasopharyngeal Carcinoma: A Large Institution-Based Cohort Study from an Endemic Area

Figures & data

Table 1 Baseline Characteristics of 2003 Patients with Nasopharyngeal Carcinoma

Characteristic	No. of Patients (%)
Age, yr
Median	45
Range	18–78
Sex
Female	507 (25.3)
Male	1496 (74.7)
Smoking
No	1284 (64.1)
Yes	719 (35.9)
Drinking
No	1759 (87.8)
Yes	244 (12.2)
Family history of Cancer
No	1432 (71.5)
Yes	571 (28.5)
Body mass index
< 25 kg/m^2	1484 (74.1)
≥ 25 kg/m^2	519 (25.9)
Hyperglycemia
No	1675 (83.6)
Yes	328 (16.4)
Hypertension
No	1711 (85.4)
Yes	292 (14.6)
Dyslipidemia
No	1283 (64.1)
Yes	720 (35.9)
Metabolic syndrome
No	1832 (91.5)
Yes	171 (8.5)
WHO type
I	9 (0.4)
II	95 (4.7)
III	1899 (94.8)
T stage*
T1	331 (16.5)
T2	333 (16.6)
T3	950 (47.4)
T4	389 (19.4)
N stage*
N0	334 (16.7)
N1	1136 (56.7)
N2	324 (16.2)
N3	209 (10.4)
TNM stage*
I	111 (5.5)
II	396 (19.8)
III	935 (46.7)
IV	561 (28.0)
PS score
0	1709 (85.3)
1	288 (14.4)
2	6 (0.3)
Chemotherapy
No	298 (14.9)
Yes	1705 (85.1)

Note: *According to the 8th AJCC/UICC staging system.

Abbreviations: WHO, World Health Organization; TNM, tumour-node-metastasis; PS, performance status, according to Eastern Cooperative Oncology Group Performance Status.

Table 2 Baseline Characteristics of Nasopharyngeal Carcinoma Patients with or without Metabolic Syndrome

Characteristic	Metabolic Syndrome		P value†
	With, n (%)	Without, n (%)
Age
≤ 45 yr	52 (30.4)	1020 (55.7)	<0.001
> 45 yr	119 (69.6)	812 (44.3)
Sex
Female	27 (15.8)	480 (26.2)	0.003
Male	144 (84.2)	1352 (73.8)
Smoking
No	100 (58.5)	1184 (64.6)	0.109
Yes	71 (41.5)	648 (35.4)
Drinking
No	151 (88.3)	1608 (87.8)	0.839
Yes	20 (11.7)	224 (12.2)
Family history of cancer
No	123 (71.9)	1309 (71.5)	0.895
Yes	48 (28.1)	523 (28.5)
WHO type
I+II	7 (4.1)	97 (5.3)	0.498
III	164 (95.9)	1735 (94.7)
T stage*
T1	22 (12.9)	311 (17.0)	0.093
T2	39 (22.8)	292 (15.9)
T3	80 (46.8)	870 (47.5)
T4	30 (17.5)	359 (19.6)
N stage*
N0	27 (15.8)	307 (16.8)	0.957
N1	96 (56.1)	1040 (56.8)
N2	30 (17.5)	294 (16.0)
N3	18 (10.5)	191 (10.4)
TNM stage*
I	6 (3.5)	105 (5.7)	0.436
II	40 (23.4)	356 (19.4)
III	79 (46.2)	856 (46.7)
IV	46 (26.9)	515 (28.1)
PS score
0	142 (83.0)	1567 (85.5)	0.463
1	29 (17.0)	259 (14.2)
2	0 (0.0)	6 (0.3)
Chemotherapy
No	26 (15.2)	272 (14.8)	0.900
Yes	145 (84.8)	1560 (85.2)

Notes: ^†P value was calculated using the chi-square test or Fisher’s exact test. *According to the 8th AJCC/UICC staging system.

Abbreviations: WHO, World Health Organization; TNM, tumour-node-metastasis; PS, performance status, according to Eastern Cooperative Oncology Group Performance Status.

Figure 1 Kaplan–Meier curve analysis of survival probabilities of NPC patients stratified by metabolic syndrome. (A) Progression-free survival. (B) Cancer specific survival. (C) Overall survival.

Abbreviation: MetS, metabolic syndrome.

Table 3 Univariate Analysis of Prognostic Factors in Patients with Nasopharyngeal Carcinoma

Variable	Univariate Analysis
	HR	95% CI	P value†
Progression-free survival
Age (≥45 years vs <45 years)	1.42	1.21–1.68	<0.001
Sex (Female vs Male)	0.81	0.66–0.99	0.037
Smoking (Yes vs No)	1.33	1.12–1.57	0.001
Drinking (Yes vs No)	1.19	0.94–1.51	0.149
Family history of cancer (Yes vs No)	0.84	0.70–1.02	0.071
Metabolic syndrome (With vs Without)	1.41	1.08–1.83	0.012
WHO type (III vs I+II)	0.61	0.45–0.84	0.002
TNM stage (III–IV vs I–II)	2.27	1.80–2.88	<0.001
Cancer-specific survival
Age (≥45 years vs <45 years)	1.43	1.17–1.76	0.001
Sex (Female vs Male)	0.79	0.62–1.01	0.058
Smoking (Yes vs No)	1.42	1.16–1.75	0.001
Drinking (Yes vs No)	1.12	0.83–1.51	0.464
Family history of cancer (Yes vs No)	0.87	0.69–1.10	0.242
Metabolic syndrome (With vs Without)	1.59	1.17–2.17	0.003
WHO type (III vs I+II)	0.51	0.36–0.72	<0.001
TNM stage (III–IV vs I–II)	3.05	2.21–4.22	<0.001
Overall survival
Age (≥45 years vs <45 years)	1.60	1.32–1.93	<0.001
Sex (Female vs Male)	0.75	0.59–0.94	0.014
Smoking (Yes vs No)	1.41	1.17–1.70	<0.001
Drinking (Yes vs No)	1.09	0.82–1.44	0.558
Family history of cancer (Yes vs No)	0.86	0.70–1.07	0.181
Metabolic syndrome (With vs Without)	1.60	1.21–2.13	0.001
WHO type (III vs I+II)	0.56	0.40–0.79	0.001
TNM stage (III–IV vs I–II)	2.93	2.18–3.93	<0.001

Note: ^†P value was calculated using the univariate Cox proportional hazards model.

Abbreviations: WHO, World Health Organization; HR, hazard ratio; 95% CI, 95% confidence interval; TNM, tumour-node-metastasis.

Table 4 Multivariable Analysis of Prognostic Factors in Patients with Nasopharyngeal Carcinoma

Variable	Multivariable Analysis
	HR	95% CI	P value†
Progression-free survival
Age (≥45 years vs <45 years)	1.32	1.11–1.56	0.001
Smoking (Yes vs No)	1.22	1.03–1.44	0.023
Metabolic syndrome (With vs Without)	1.34	1.03–1.75	0.032
WHO type (III vs I+II)	0.60	0.44–0.83	0.002
TNM stage (III–IV vs I–II)	2.25	1.78–2.85	<0.001
Cancer-specific survival
Age (≥45 years vs <45 years)	1.29	1.05–1.60	0.016
Smoking (Yes vs No)	1.30	1.06–1.60	0.013
Metabolic syndrome (With vs Without)	1.53	1.12–2.08	0.008
WHO type (III vs I+II)	0.49	0.35–0.70	<0.001
TNM stage (III–IV vs I–II)	3.03	2.19–4.19	<0.001
Overall survival
Age (≥45 years vs <45 years)	1.45	1.20–1.76	<0.001
Smoking (Yes vs No)	1.27	1.05–1.53	0.016
Metabolic syndrome (With vs Without)	1.50	1.13–2.00	0.006
WHO type (III vs I+II)	0.55	0.39–0.78	0.001
TNM stage (III–IV vs I–II)	2.89	2.15–3.88	<0.001

Note: †P value was calculated using the multivariable Cox proportional hazards model. The following parameters were included in the Cox proportion hazard model by backward elimination: age (≥45 vs <45 years), sex (Female vs Male), smoking (Yes vs No), drinking (Yes vs No), family history of cancer (Yes vs No), metabolic syndrome (With vs Without), WHO type (Type III vs Type I+II), and TNM stage (III–IV vs I–II) as covariates. Only variables significantly related to survival are presented.

Abbreviations: WHO, World Health Organization; HR, hazard ratio; 95% CI, 95% confidence interval; TNM, tumour-node-metastasis.

Figure 2 Metabolic profile analysis of NPC patients with and without metabolic syndrome. (A) Partial least-squares discrimination analysis (PLS-DA) of the serum metabolomic file of NPC patients in the MetS and NMetS groups (n = 5). Each symbol represents the data of an individual patient. (B) Fold change analysis discovering differential serum metabolites, which were identified with a log₂ (FC) of MetS/NMetS > 1 or < −1. (C) Heatmap showing the top 50 differential serum metabolites. Differential serum metabolites were identified with p<0.05 using Student’s t-test.

Abbreviations: MetS, metabolic syndrome; NMetS, non-metabolic syndrome.

Figure 3 Enrichment and pathway analysis of differential metabolites. (A) Bar plot of KEGG pathway analysis of differential metabolites; (B) dot plot of KEGG pathway analysis of differential metabolites.