Ferritin as a novel predictive index for nasopharyngeal carcinoma survival and therapeutic efficacy of different chemotherapy regimens

Table 1 Baseline characteristics between survivors and non-survivors, n (%)

Variable	Total (n = 1142)	Survivors (n = 615)	Non-survivors (n = 527)	Statistic	P value
Gender
Male	783 (68.56)	407 (66.18)	376 (71.35)
Female	359 (31.44)	208 (33.82)	151 (28.65)
Age (years)
≤ 29	47 (4.12)	36 (76.60)	11 (23.40)
30-39	202 (17.69)	132 (65.35)	70 (34.65)
40-49	522 (45.70)	268 (51.34)	254 (48.66)
50-59	279 (24.43)	138 (49.46)	141 (50.54)
60-69	88 (7.71)	41 (46.59)	47 (53.41)
≥ 70	4 (0.35)	0 (0)	4 (100)
Tumor stage (%)				χ² = 6.08	0.193
I	0.47	0.73	0.23
II	5.44	7.07	3.90
III	54.61	56.65	52.44
IVa	35.46	34.86	36.10
IVb	4.02	3.66	4.36
TAM (U/mL)	89.27 ± 12.43	87.73 ± 11.09	90.89 ± 13.60	t = 1.42	0.159
TSGF (U/mL)	54.40 ± 17.22	54.37 ± 17.19	54.43 ± 17.28	t = 0.05	0.959
NSE (ng/mL)	2.61 ± 1.95	2.55 ± 2.11	2.68 ± 1.79	t = 0.61	0.539
CEA (mg/L)	1.41 ± 1.48	1.22 ± 0.95	1.58 ± 1.83	t = 2.36	0.019
Feritin (ng/mL)	133.42 ± 76.11	97.32 ± 68.38	167.22 ± 67.04	t = 9.84	< 0.001
AFP (ng/mL)	1.73 ± 2.09	1.65 ± 2.12	1.82 ± 2.05	t = 0.77	0.444
AST (U/L)	23.45 ± 16.30	23.58 ± 17.14	23.30 ± 15.35	t = -0.26	0.798
ALT (U/L)	26.83 ± 29.59	27.39 ± 29.30	26.22 ± 29.93	t = -0.60	0.547
ALP (U/L)	75.67 ± 27.43	75.33 ± 28.26	76.04 ± 26.52	t = 0.38	0.706
LDH (U/L)	172.59 ± 42.86	169.30 ± 42.23	176.27 ± 43.32	t = 2.36	0.018
GGT (U/L)	33.87 ± 53.87	31.13 ± 27.63	36.90 ± 72.44	t = 1.55	0.122
5-NT (U/L)	6.07 ± 5.51	5.91 ± 5.14	6.25 ± 5.89	t = 0.89	0.371
GPDA (U/L)	67.91 ± 21.38	68.18 ± 20.06	67.61 ± 22.76	t = -0.38	0.704
ADA (U/L)	15.18 ± 23.80	14.58 ± 17.97	15.83 ± 28.91	t = 0.75	0.450
MAO (U/L)	4.77 ± 2.37	4.75 ± 2.33	4.80 ± 2.41	t = 0.26	0.794

TAM: Tumor-associated material; TSGF: Tumor-supplied group of factors; NSE: Neuron-specific enolase; CEA: Carcinoembryonic antigen; AFP: Alpha-fetoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; LDH: Lactate dehydrogenase; GGT: Gamma-glutamyl transferase; 5-NT: 5'-Nucleotidase; GPDA: Glycyl-proline-dipeptidyl aminopeptidase; ADA: Adenosine deaminase; MAO: Monoamine oxidase.

Table 2 Chemotherapy regimens and laboratory indicator between survivors and non-survivors after treatment

Variable	Total (n = 1142)	Survivors (n = 615)	P (vs pre-treatment)	Non-survivors (n = 527)	P (vs pre-treatment)	Statistic	P (survivors vs non-survivors)
TAM	90.30 ± 13.46	91.48 ± 13.35	0.587	88.69 ± 13.59	0.561	t = -1.09	0.278
TSGF	58.64 ± 18.46	57.93 ± 19.17	0.739	59.45 ± 17.62	0.164	t = 0.99	0.325
AST	22.91 ± 11.72	23.08 ± 11.34	0.732	22.71 ± 12.17	0.819	t = -0.40	0.689
ALT	24.48 ± 23.25	25.35 ± 25.70	0.433	23.49 ± 20.04	0.610	t = -1.02	0.309
ALP	69.73 ± 21.94	69.66 ± 20.91	0.577	69.81 ± 23.10	0.778	t = 0.08	0.936
LDH	165.50 ± 39.74	164.23 ± 36.81	0.058	166.94 ± 42.84	0.970	t = 0.82	0.411
GGT	29.74 ± 29.49	30.14 ± 27.92	0.187	29.29 ± 31.22	0.899	t = -0.35	0.729
5-NT	5.32 ± 4.45	5.04 ± 3.91	0.639	5.63 ± 4.98	0.136	t = 1.59	0.113
GPDA	61.76 ± 18.61	61.99 ± 18.50	0.785	61.51 ± 18.78	0.773	t = -0.31	0.759
ADA	14.50 ± 16.11	14.35 ± 20.03	0.516	14.68 ± 9.95	0.929	t = 0.24	0.809
MAO	4.21 ± 2.47	4.15 ± 2.55	0.801	4.28 ± 2.38	0.856	t = 0.59	0.552
NSE	2.76 ± 1.91	2.78 ± 1.87	0.875	2.74 ± 1.96	0.772	t = -0.24	0.812
CEA	1.74 ± 6.55	1.41 ± 1.10	0.054	2.16 ± 9.71	0.275	t = 1.24	0.215
FERITIN	94.80 ± 78.43	59.86 ± 31.90	< 0.001a	138.57 ± 95.67	< 0.001a	t = 11.43	< 0.001a
AFP	2.43 ± 5.28	2.32 ± 3.18	0.658	2.57 ± 7.08	0.666	t = 0.52	0.604
Treatment, (%)						-	0.5701
CAV	0.10	0.19		0.00
CNF	0.10	0.00		0.21
DF	0.10	0.19		0.00
DGP	0.10	0.19		0.00
DN	7.98	7.41		8.61
DNF	0.50	0.38		0.63
DNL	0.10	0.19		0.00
DP	4.49	3.80		5.25
DPF	1.50	1.52		1.47
DPN	0.10	0.19		0.00
DPS	0.10	0.19		0.00
GN	0.40	0.38		0.42
GP	0.60	0.76		0.42
NF	16.17	16.35		15.97
NP	0.10	0.19		0.00
NPF	0.50	0.57		0.42
PF	12.87	10.08		15.97
TDP	0.20	0.19		0.21
TF	0.10	0.19		0.00
TN	16.07	16.16		15.97
TNF	2.30	2.66		1.89
TP	18.96	19.77		18.07
TPF	1.80	2.09		1.47
TPN	0.10	0.00		0.21
Radiotherapy	13.17	14.45		11.76
Radiotherapy plus chemotherapy	0.90	1.14		0.63
Surgery	0.10	0.00		0.21
Surgery plus radiotherapy	0.50	0.76		0.21

¹Simulated P value.

^aP < 0.05.

t: T-test, Fisher’s exact test. TAM: Tumor-associated material; TSGF: Tumor-supplied group of factors; NSE: Neuron-specific enolase; CEA: Carcinoembryonic antigen; AFP: Alpha-fetoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; LDH: Lactate dehydrogenase; GGT: Gamma-glutamyl transferase; 5-NT: 5'-Nucleotidase; GPDA: Glycyl-proline-dipeptidyl aminopeptidase; ADA: Adenosine deaminase; MAO: Monoamine oxidase; CAV: Cyclophosphamide, doxorubicin plus etoposide; CNF: Cyclophosphamide, nidaplatin plus 5-FU; DF: Docetaxel plus 5-FU; DGP: Docetaxel, gemcitabine plus cisplatin; DN: Docetaxel plus nedaplatin; DNF: Docetaxel, nidaplatin plus 5-FU; DNL: Docetaxel, nidaplatin plus leucovorin; DP: Docetaxel plus cisplatin; DPF: Docetaxel, cisplatin plus 5-FU; DPN: Docetaxel, cisplatin plus nedaplatin; DPS: Docetaxel, cisplatin plus teysuno; GN: Gemcitabine plus nedaplatin; GP: Gemcitabine plus cisplatin; NF: Nidaplatin plus 5-FU; NP: Nidaplatin plus cisplatin; NPF: Nidaplatin, cisplatin plus 5-FU; PF: Cisplatin plus 5-FU; TDP: Taxol, docetaxel plus cisplatin; TF: Taxol, plus 5-FU; TN: Taxol plus nedaplatin; TNF: Taxol, nidaplatin plus 5-FU; TP: Taxol plus cisplatin; TPF: Taxol, cisplatin plus 5-FU; TPN: Taxol, cisplatin plus nedaplatin.

Table 3 Weighted baseline characteristics by quartiles of the Ferritin index

Ferritin index	Quartile 1 (1.89-83.13)	Quartile 2 (83.18-129.21)	Quartile 3 (130.65-175.25)	Quartile 4 (175.68-378.29)	Statistic	P value
Age	44.31 ± 10.51	45.90 ± 11.01	46.95 ± 9.46	47.66 ± 8.70	F = 1.94	0.122
TAM	92.71 ± 11.71	96.23 ± 14.10	90.62 ± 11.22	91.41 ± 14.77	F = 0.56	0.645
TSGF	52.11 ± 15.94	52.25 ± 18.33	51.70 ± 17.98	54.60 ± 18.68	F = 0.42	0.736
AST	22.16 ± 7.34	23.52 ± 26.25	23.61 ± 9.15	23.78 ± 14.54	F = 0.19	0.902
ALT	22.07 ± 13.33	29.38 ± 55.16	27.47 ± 18.35	27.73 ± 23.93	F = 0.88	0.453
ALP	75.24 ± 35.52	75.57 ± 23.04	74.70 ± 17.44	83.76 ± 42.89	F = 1.47	0.222
LDH	175.75 ± 46.90	167.67 ± 45.76	173.61 ± 40.56	179.49 ± 51.28	F = 0.93	0.428
GGT	27.34 ± 25.41	36.67 ± 50.42	37.54 ± 39.92	54.94 ± 146.71	F = 1.63	0.182
5-NT	5.66 ± 4.42	6.24 ± 5.18	6.39 ± 4.82	6.94 ± 7.87	F = 0.67	0.571
GPDA	70.79 ± 20.37	65.42 ± 25.22	72.53 ± 23.03	74.70 ± 28.84	F = 2.11	0.099
ADA	13.85 ± 7.51	15.42 ± 14.51	16.90 ± 18.88	13.91 ± 9.46	F = 0.93	0.426
MAO	4.71 ± 2.50	4.78 ± 2.00	5.30 ± 2.58	5.12 ± 2.72	F = 1.02	0.385
NSE	2.07 ± 1.30	2.64 ± 1.61	2.88 ± 2.08	2.88 ± 2.51	F = 3.55	0.015a
CEA	1.13 ± 0.79	1.57 ± 2.22	1.36 ± 1.07	1.58 ± 1.43	F = 1.91	0.127
AFP	1.28 ± 1.13	1.94 ± 2.91	2.01 ± 2.12	1.71 ± 1.76	F = 2.29	0.078
Tumor stage (%)					-	0.838
I	0	0	0	0
II	5.06	6.10	4.94	5.13
III	54.43	54.88	54.32	42.31
IVa	36.71	34.15	35.80	43.59
IVb	3.80	4.88	4.94	8.97
Gender (%)					χ² = 44.94	< 0.001a
Male	41.76	76.92	82.42	76.92
Female	58.24	23.08	17.58	23.08
3-year survivors (%)					χ² = 34.13	< 0.001a
Death	3.30	29.67	31.87	38.46
Survival	96.70	70.33	68.13	61.54
5-year survivors (%)					χ² = 97.78	< 0.001a
Death	8.79	62.64	57.14	78.02
Survival	91.21	37.36	42.86	21.98

^aP < 0.05.

F: ANOVA. -: Fisher’s exact test. TAM: Tumor-associated material; TSGF: Tumor-supplied group of factors; NSE: Neuron-specific enolase; CEA: Carcinoembryonic antigen; AFP: Alpha-fetoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; LDH: Lactate dehydrogenase; GGT: Gamma-glutamyl transferase; 5-NT: 5'-Nucleotidase; GPDA: Glycyl-proline-dipeptidyl aminopeptidase; ADA: Adenosine deaminase; MAO: Monoamine oxidase.

Table 4 Association between Ferritin index related indicators and 5-year mortality (Cox regression)

Variable	Model 1		Model 2		Model 3
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Continuous Ferritin value	0.99 (0.99-0.99)	< 0.001a	0.99 (0.99-0.99)	< 0.001a	1.03 (1.01-1.05)	0.046a
Ferritin quartile
1	1.00 (reference)		1.00 (reference)		1.00 (reference)
2	0.27 (0.18-0.40)	< 0.001a	0.18 (0.10-0.31)	< 0.001a	0.01 (0.00-0.02)	< 0.001a
3	0.36 (0.24-0.52)	< 0.001a	0.32 (0.19-0.54)	< 0.001a	0.02 (0.01-0.05)	< 0.001a
4	0.21 (0.13-0.34)	< 0.001a	0.16 (0.08-0.30)	< 0.001a	19.19 (6.15-59.88)	< 0.001a

^aP < 0.05.

Model 1: Crude. Model 2: Adjusted for age and sex. Model 3: Adjusted for age, sex, tumor stage, tumor associated material, tumor supplied group of factors, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, glycyl-proline-dipeptidyl aminopeptidase, and neuron-specific enolase levels. HR: Hazard ratio.

Table 5 Association of Ferritin index-related indicator with 3-year mortality (Cox regression)

Variable	Model 1		Model 2		Model 3
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
Continuous Ferritin value	0.99 (0.99-0.99)	< 0.001a	1.00 (1.00-1.00)	0.058	1.03 (1.02-1.03)	< 0.001a
Ferritin quartile
1	1.00 (reference)		1.00 (reference)		1.00 (reference)
2	0.49 (0.35-0.67)	< 0.001a	0.42 (0.27-0.65)	< 0.001a	0.25 (0.11-0.60)	0.002a
3	0.54 (0.39-0.76)	< 0.001a	0.60 (0.39-0.92)	0.019a	0.58 (0.27-1.22)	0.151
4	0.55 (0.39-0.77)	< 0.001a	0.58 (0.37-0.91)	0.018a	399.19 (175.20-909.51)	< 0.001a

^aP < 0.05.

Model 1: Crude. Model 2: Adjusted for age and sex. Model 3: Adjusted for age, sex, tumor stage, tumor associated material, tumor supplied group of factors, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, glycyl-proline-dipeptidyl aminopeptidase, and neuron-specific enolase levels. HR: Hazard ratio.