Thyroid hormones as biomarkers of lung cancer: a retrospective study

Figures & data

Table 1. Clinicopathological data of all patients and healthy subjects included in the study.

Variables	Healthy subjects	Lung cancer patients A	Lung cancer patients B
Athnicity	Asians	Asians	Asians
Age
Mean ± SD	65.09 ± 0.700	66.82 ± 0.655	65.77 ± 0.181
Sex
Female	55	46	43
Male	183	159	41
Tumor type
SCLC		51	1
NSCLC		154	83
Tumor size (maximum diametercm)
≤4 cm		93	84
>4 cm		112	0
Lymph node metastasis
Positive		179	0
Negative		26	84
TMN stage
0		0	84
I/II/III		81	0
IV		124	0

Figure 1. Flow diagram showing the study process.

Figure 2. Serum thyroid hormones concentrations in lung cancer patients and their clinical significance. (A) Serum concentration of thyroid stimulating hormone (TSH) in lung cancer patients (n = 205) and healthy subjects (n = 238). (B) Serum concentration of total thyroxine (TT4) in lung cancer patients (n = 205) and healthy subjects (n = 238). (C) Serum concentration of total triiodothyronine (TT3) in lung cancer patients (n = 205) and healthy subjects (n = 238). (D) Serum concentration of free thyroxine (FT4) in lung cancer patients (n = 205) and healthy subjects (n = 238). (E) Serum concentration of free triiodothyronine (FT3) in lung cancer patients (n = 205) and healthy subjects (n = 238). Data are shown as the mean ± SD.

Table 2. Association of serum thyroid hormones levels with clinicopathological parameters of patients A group with lung cancer.

		Serum TSH level
		Low	High
Variables	No of cases	n = 129	n = 76	p
Age (year, mean = 66.8)				0.15
<67	94	64	30
≥67	111	65	46
Sex				0.17
Men	159	104	55
Women	46	25	21
Tumor type				0.3
SCLC	51	29	22
NSCLC	154	100	54
Tumor size (maximum diametercm)				0.82
≤4 cm	93	59	36
>4 cm	112	70	40
Lymph node metastasis				0.48
Positive	179	113	69
Negative	26	16	7
TMN stage				1.0
I/II/III	81	51	30
IV	124	78	46
		Serum TT4 level
		Low	High
Variables	No of cases	n = 106	n = 99	p
Age (year, mean = 66.8)
<67	94	46	48	0.465
≥67	111	60	51
Sex
Men	159	85	74	0.350
Women	46	21	25
Tumor type
SCLC	51	24	27	0.443
NSCLC	154	82	72
Tumor size (maximum diametercm)				0.087
≤4 cm	93	42	51
>4 cm	112	64	48
Lymph node metastasis
Positive	179	96	83	0.148
Negative	26	10	16
TMN stage				0.26
I/II/III	81	38	43
IV	124	68	56
		Serum TT3 level
		Low	High
Variables	No of cases	n = 98	n = 107	p
Age (year, mean = 66.8)
<67	94	31	63	0.01
≥67	111	67	44
Sex
Men	159	76	83	0.01
Women	46	53	21
Tumor type
SCLC	51	21	30	0.274
NSCLC	154	77	77
Tumor size (maximum diametercm)				0.036
≤4 cm	93	37	56
>4 cm	112	61	51
Lymph node metastasis
Positive	179	91	88	0.022
Negative	26	7	19
TMN stage				0.836
I/II/III	81	38	43
IV	124	60	64
		Serum FT4 level
		Low	High
Variables	No of cases	n = 107	n = 98	p
Age (year, mean = 66.8)
<67	94	54	40	0.166
≥67	111	53	58
Sex
Men	159	84	75	0.735
Women	46	23	23
Tumor type
SCLC	51	24	27	0.397
NSCLC	154	83	71
Tumor size (maximum diametercm)				0.665
≤4 cm	93	47	46
>4 cm	112	60	52
Lymph node metastasis
Positive	179	94	85	0.810
Negative	26	13	13
TMN stage				0.001
I/II/III	81	54	27
IV	124	53	71
		Serum FT3 level
		Low	High
Variables	No of cases	n = 98	n = 107	p
Age (year, mean = 66.8)
<67	94	34	60	0.002
≥67	111	64	47
Sex
Men	159	76	83	1.0
Women	46	22	24
Tumor type
SCLC	51	19	32	0.08
NSCLC	154	79	75
Tumor size (maximum diametercm)				0.003
≤4 cm	93	34	59
>4 cm	112	64	48
Lymph node metastasis
Positive	179	86	93	0.855
Negative	26	12	14
TMN stage				0.436
I/II/III	81	36	45
IV	124	62	62

Figure 3. The receiver operating curve (ROC) for the prediction of stage 0 and I–IV lung cancer based on the serum concentration of thyroid hormones and traditional lung cancer markers, using paired healthy subjects as control. (A) ROC curve showing the diagnostic significance of serum thyroid stimulating hormone (TSH) concentration in the lung cancer patients A group. (B) ROC curve showing the diagnostic significance of serum total thyroxine (TT4) concentration in the lung cancer patients A group. (C) ROC curve showing the diagnostic significance of serum total triiodothyronine (TT3) concentration in the lung cancer patients A group. (D) ROC curve showing the diagnostic significance of serum free thyroxine (FT4) level in the lung cancer patients A group. (E) ROC curve showing the diagnostic significance of serum free triiodothyronine (FT3) level in the lung cancer patients A group. (F) ROC curve showed the diagnostic significance of serum carcinoma embryonic antigen (CEA) concentration in the lung cancer patients A group. (G) ROC curve showing the diagnostic significance of serum squamous cell carcinoma (SCC) concentration in the lung cancer patients A group. (H) ROC curve showing the diagnostic significance of serum neuron specific enolase (NSE) concentration in the lung cancer patients A group. (I) ROC curve showing the diagnostic significance of serum CYFRA21-1 (CYF) concentration in the lung cancer patients A group. (J) Comparison of ROC curve showing the diagnostic significance of serum CEA, CYFRA21-1 (CYF) and FT3 concentration in the lung cancer patients A group. (K) Comparison of ROC curve showing the diagnostic significance of serum CEA, CYFRA21-1 (CYF), FT3 and FT3 + CEA + CYF concentration in the lung cancer patients A group. (L) ROC curve showing the diagnostic significance of serum free triiodothyronine (FT3) level in the lung cancer patients B group. (M) ROC curve showing the diagnostic significance of serum free thyroxine (FT4) level in the lung cancer patients B group. (N) ROC curve showed the diagnostic significance of serum carcinoma embryonic antigen (CEA) concentration in the lung cancer patients B group. (O) Comparison of ROC curve showing the diagnostic significance of serum CEA, FT3 and FT4 concentration in the lung cancer patients B group. (P) Comparison of ROC curve showing the diagnostic significance of serum CEA, FT3, FT4 and FT3 + FT4 + CEA concentration in the lung cancer patients B group.

Figure 4. The sensitivity and specificity of markers to differentiate lung cancer patients with different TNM stage from healthy subjects. (A) The sensitivity, specificity and cut-off value of TSH concentration in the lung cancer patients A group. (B) The sensitivity, specificity and cut-off value of TT4 concentration in the lung cancer patients A group. (C) The sensitivity, specificity and cut-off value of TT3 concentration in the lung cancer patients A group. (D) The sensitivity, specificity and cut-off value of FT4 concentration in the lung cancer patients A group. (E) The sensitivity, specificity and cut-off value of FT3 concentration in the lung cancer patients A group. (F) The sensitivity, specificity and cut-off value of CEA concentration in the lung cancer patients A group. (G) The sensitivity, specificity and cut-off value of SCC concentration in the lung cancer patients A group. (H) The sensitivity, specificity and cut-off value of NSE concentration in the lung cancer patients A group. (I) The sensitivity, specificity and cut-off value of CYF concentration in the lung cancer patients A group. (J) The sensitivity, specificity and cut-off value of FT3 concentration in the lung cancer patients B group. (K) The sensitivity, specificity and cut-off value of FT4 concentration in the lung cancer patients B group. (L) The sensitivity, specificity and cut-off value of CEA concentration in the lung cancer patients B group.

Table 3. The assessment of a biomarker role of the thyroid hormones and traditional lung cancer markers in lung cancer.

Markers	Sensitivity (%)	Specificity (%)	AUC	Stage
TSH	59.00	52.10	0.566	I–IV
TT3	43.41	83.61	0.638	I–IV
TT4	39	85.30	0.650	I–IV
FT3	75.60	76.10	0.807	I–IV
FT4	66.83	69.33	0.731	I–IV
CEA	73	88.60	0.879	I–IV
NSE	52.20	98.30	0.753	I–IV
SCC	34.60	100	0.575	I–IV
CYF	66.20	99.20	0.876	I–IV
CEA + CYF + FT3	85.90	97.50	0.962	I–IV
TSH	65.48	42.44	0.500	0
TT3	84.52	21.43	0.518	0
TT4	64.30	60.90	0.518	0
FT3	81.00	52.90	0.678	0
FT4	56.00	64.30	0.630	0
CEA	51.20	68.90	0.616	0
NSE	73.80	35.70	0.531	0
SCC	26.20	89.90	0.591	0
CYF	40.50	82.40	0.623	0
CEA + FT4 + FT3	70.20	75.20	0.774	0

Data availability statement

Original data will be provided upon request after removal of personal identifiers.