Fibrinogen-to-Neutrophil Ratio as a New Predictor of Central Lymph Node Metastasis in Patients with Papillary Thyroid Cancer and Type 2 Diabetes Mellitus

Figures & data

Table 1 Baseline Characteristics of the Training Dataset and the External Validation Dataset

Variables	Training Dataset N=292	Validation Dataset N=121	P-value
Age
>55Y	165	66	0.715
≤55Y	127	55
Gender
Female	200	72	0.08
Male	92	49
Medicine for diabetes
Metformin (-)	149	64	0.73
Metformin (+)	143	57
BMI (kg/m^2)
>29.7	28	9	0.486
≤29.7	264	112
Maximum diameter of mass
>9.5 mm	106	34	0.109
≤9.5 mm	186	87
Multifocality
Solitary	206	83	0.694
Multiple	86	38
CLNM
CLNM (-)	161	70	0.613
CLNM (+)	131	51
Laterality
Unilateral	245	103	0.757
Bilateral	47	18
Hashimoto’s thyroiditis
Absent	259	106	0.752
Present	33	15
TC (mmol/L)
>5.585	75	26	0.366
≤5.585	217	95
TG (mmol/L)
>2.325	101	41	0.891
≤2.325	191	80
HDL (mmol/L)
>1.245	76	30	0.794
≤1.245	216	91
LDL (mmol/L)
>2.755	117	42	0.308
≤2.755	175	79
Glucose (mmol/L)
>6.1	231	98	0.665
≤6.1	61	23
Albumin (g/L)
>38.95	260	110	0.572
≤38.95	32	11
Globulin (g/L)
>32.15	92	37	0.853
≤32.15	200	84
AGR
>1.45	137	54	0.671
≤1.45	155	67
Neutrophil (x10^9/L)
>4.395	96	42	0.719
≤4.395	196	79
Mononuclear (x10^9/L)
>0.355	187	79	0.809
≤0.355	105	42
Lymphocyte (x10^9/L)
>1.695	206	85	0.951
≤1.695	86	36
Lymphocyte (%)
>28.1	194	83	0.671
≤28.1	98	38
Platelet (x10^9/L)
>255	105	41	0.688
≤255	187	80
TSH (mIU/L)
>0.86	231	96	0.958
≤0.86	61	25
T4 (pmol/L)
>11.94	82	32	0.735
≤11.94	210	89
T3 (pmol/L)
>4.775	176	72	0.884
≤4.775	116	49
FNR
>0.774	181	78	0.636
≤0.774	111	43

Abbreviations: CLNM, central lymph node metastasis; AGR, albumin globulin ratio; FNR, fibrinogen-to-neutrophil ratio.

Table 2 Correlations Between FNR and Clinical Characteristics in All Cohorts

Variables	FNR≤0.774 N=154	FNR>0.774 N=259	P-value
Age
>55Y	73	158	0.007
≤55Y	81	101
Gender
Female	95	177	0.168
Male	59	82
Medicine for diabetes
Metformin (-)	70	143	0.055
Metformin (+)	84	116
BMI (kg/m^2)
>29.7	18	19	0.134
≤29.7	136	240
Maximum diameter of mass
>9.5 mm	43	97	0.048
≤9.5 mm	111	162
Multifocality
Solitary	99	190	0.052
Multiple	55	69
CLNM
CLNM (-)	81	150	0.293
CLNM (+)	73	109
Laterality
Unilateral	131	217	0.73
Bilateral	23	42
Hashimoto’s thyroiditis
Absent	140	225	0.216
Present	14	34
TC (mmol/L)
>5.585	40	61	0.58
≤5.585	114	198
TG (mmol/L)
>2.325	60	82	0.131
≤2.325	94	177
HDL (mmol/L)
>1.245	40	66	0.912
≤1.245	114	193
LDL (mmol/L)
>2.755	63	96	0.438
≤2.755	91	163
Glucose (mmol/L)
>6.1	116	213	0.091
≤6.1	38	46
Albumin (g/L)
>38.95	140	230	0.498
≤38.95	14	29
Globulin (g/L)
>32.15	42	87	0.18
≤32.15	112	172
AGR
>1.45	73	118	0.716
≤1.45	81	141
Neutrophil (x10^9/L)
>4.395	105	33	<0.001
≤4.395	49	226
Mononuclear (x10^9/L)
>0.355	117	149	<0.001
≤0.355	37	110
Lymphocyte (x10^9/L)
>1.695	113	178	0.316
≤1.695	41	81
Lymphocyte (%)
>28.1	71	206	<0.001
≤28.1	83	53
Platelet (x10^9/L)
>255	61	85	0.163
≤255	93	174
TSH (mIU/L)
>0.86	115	212	0.082
≤0.86	39	47
T4 (pmol/L)
>11.94	42	72	0.908
≤11.94	112	187
T3 (pmol/L)
>4.775	106	142	0.005
≤4.775	48	117
Fibrinogen (g/L)
>3.145	65	183	<0.001
≤3.145	89	76

Abbreviations: CLNM, central lymph node metastasis; AGR, albumin globulin ratio.

Table 3 Univariate and Multivariate Analysis of Logistic Regression in the Training Data Set

Variables	Univariate Analysis of CLNM			Multivariate Analysis of CLNM
	OR	95% CI	P-value	OR	95% CI	P-value
Age	0.871	0.479–1.585	0.651
>55Y
≤55Y
Gender	0.943	0.483–1.841	0.862
Female
Male
Medicine for diabetes	0.606	0.341–1.076	0.087	0.594	0.347–1.015	0.057
Metformin (-)
Metformin (+)
BMI (kg/m^2)	1.705	0.617–4.715	0.304
>29.7
≤29.7
Maximum diameter of mass	6.919	3.637–13.160	<0.001	6.055	3.391–10.811	<0.001
>9.5 mm
≤9.5 mm
Multifocality	0.731	0.378–1.411	0.35
Solitary
Multiple
Laterality	1.041	0.461–2.349	0.923
Unilateral
Bilateral
Hashimoto’s thyroiditis	1.25	0.514–3.043	0.622
Absent
Present
TC (mmol/L)	1.216	0.519–2.852	0.653
>5.585
≤5.585
TG (mmol/L)	0.28	0.136–0.579	0.001	0.349	0.189–0.647	0.001
>2.325
≤2.325
HDL (mmol/L)	0.377	0.182–0.783	0.009	0.316	0.164–0.612	0.001
>1.245
≤1.245
LDL (mmol/L)	0.72	0.354–1.463	0.363
>2.755
≤2.755
Glucose (mmol/L)	1.358	0.646–2.852	0.42
>6.1
≤6.1
Albumin (g/L)	0.653	0.252–1.696	0.382
>38.95
≤38.95
Globulin (g/L)	0.56	0.262–1.199	0.136
>32.15
≤32.15
AGR	0.661	0.318–1.374	0.267
>1.45
≤1.45
Mononuclear (x10^9/L)	1.577	0.802–3.103	0.187
>0.355
≤0.355
Lymphocyte (x10^9/L)	0.45	0.216–0.935	0.032	0.539	0.297–0.978	0.042
>1.695
≤1.695
Lymphocyte (%)	1.396	0.671–2.906	0.372
>28.1
≤28.1
Platelet (x10^9/L)	0.765	0.403–1.454	0.414
>255
≤255
TSH (mIU/L)	1.344	0.648–2.789	0.427
>0.86
≤0.86
T4 (pmol/L)	0.573	0.296–1.110	0.099	0.539	0.292–0.996	0.049
>11.94
≤11.94
T3 (pmol/L)	0.715	0.389–1.314	0.279
>4.775
≤4.775
FNR	0.47	0.239–0.923	0.028	0.494	0.282–0.868	0.014
>3.145
≤3.145

Abbreviations: CLNM, central lymph node metastasis; FNR, fibrinogen-to-neutrophil ratio.

Figure 1 Nomogram for predicting CLNM in patients with T2DM PTC.

Abbreviation: FNR, fibrinogen-to-neutrophil ratio.

Figure 2 Receiver operating characteristic (ROC) curve analysis. (A) Training dataset. (B) External validation dataset.

Figure 3 Calibration curve of the nomogram. (A) Training dataset. (B) External validation dataset.

Figure 4 Decision curve analysis (DCA) of nomogram. (A) Training dataset. (B) External validation dataset.

Figure 5 Comparison with original model. (A) Receiver operating characteristic (ROC) curve analysis. (B) Net reclassification index (NRI).