Correlation Between Serum Tumor Marker Levels and Connective Tissue Disease-Related Interstitial Lung Disease

Figures & data

Table 1 Demographic and Clinical Characteristics of Study Participants

	CTD-ILD (n=145)	CTDs without ILDs (n=90)	p value
Mean age, years (SD)	58.52 (11.88)	56.17 (15.16)	0.213
Sex, female (%)	98 (67.6%)	65 (72.2%)	0.546
Type of CTD (n, %)			0.082
RA	91 (62.8%)	60 (66.7%)
SS	19 (13.1%)	11 (12.2%)
SLE	13 (8.9%)	13 (14.4%)
IM	11 (7.6%)	0
Others (SSc or MCTD)	11 (7.6%)	6 (6.7%)
Inflammatory markers (SD)
Mean ESR, mm/h	57.43 (35.67)	56.10 (34.16)	0.776
Mean CRP, mg/dL	30.92 (36.52)	33.68 (39.23)	0.591

Abbreviations: CTDs, connective tissue diseases; ILDs, interstitial lung diseases; CTD-ILD, connective tissue disease-related interstitial lung disease; RA, rheumatoid arthritis; SS, Sjogren’s syndrome; SLE, systemic lupus erythematosus; IM, inflammatory myositis; SSc, systemic sclerosis; MCTD, mixed connective tissue disease; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Table 2 Comparison of Tumor Markers Levels Among Two Groups

Tumor Markers [Median (Range)]	CTD-ILD	CTDs without ILDs	p value
CA19-9, U/mL	7.3 (0.0, 54)	4.8 (0.0, 25.6)	<0.001
CA125, U/mL	14.8 (3.2, 95.7)	14.4 (5.4, 42.5)	0.146
CEA, ng/mL	1.73 (0.34, 8.36)	1.07 (0.24, 6.34)	<0.001
CA153, U/mL	10.6 (2.8, 36.6)	6.6 (3.2, 26.5)	<0.001
CYFRA21-1, ng/mL	2.32 (0.56, 7.54)	1.62 (0.33, 4.67)	<0.001

Abbreviations: CTDs, connective tissue diseases; ILDs, interstitial lung diseases; CTD-ILD, connective tissue disease-related interstitial lung disease; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; CYFRA21-1, cytokeratin 19 fragment.

Figure 1 Levels of tumor markers in patients with CTDs with or without ILDs, including CA19-9 (A), CA125 (B), CEA (C), CA153 (D), and CYFRA21-1 (E).

Table 3 Tumor Markers According to the Presence of ILDs in Each CTDs

Tumor Markers [Median (Range)]	RA-ILD (n=91)	SS-ILD (n=19)	SLE-ILD (n=13)	IM-ILD (n=11)	Other CTD-ILD (n=11)	p value
CA19-9, U/mL	7.4 (0.0, 50.5)	9.6 (0.6, 54)	3.3 (0.4, 52.1)	6.8 (0.0, 26.9)	4.1 (0.0, 18.2)	0.080
CA125, U/mL	19.1 (3.4, 85.3)	12.7 (3.2, 36.7)	13.1 (5.4, 95.7)	10.9 (4.3, 69.1)	23 (8.1, 29.8)	0.346
CEA, ng/mL	1.73 (0.42, 8.36)	1.97 (0.58, 2.84)	0.92 (0.34, 6.55)	1.15 (0.64, 4.78)	2.36 (0.65, 3.51)	0.142
CA153, U/mL	10.6 (4, 24.9)	11.8 (2.8, 28.3)	8.5 (4.7, 19.4)	11.1 (7, 36.6)	8.2 (4.7, 20.5)	0.686
CYFRA21-1, ng/mL	2.36 (0.56, 7.54)	2.32 (1.14, 4.20)	2.42 (0.84, 3.68)	2.31 (1.54, 4.57)	2.25 (0.96, 3.76)	0.938

Abbreviations: CTDs, connective tissue diseases; ILDs, interstitial lung diseases; CTD-ILD, connective tissue disease-related interstitial lung disease; RA, rheumatoid arthritis; SS, Sjogren’s syndrome; SLE, systemic lupus erythematosus; IM, inflammatory myositis; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; CYFRA21-1, cytokeratin 19 fragment.

Table 4 Spearman Correlation Coefficient Values of Tumor Markers and Disease Characteristics of CTDs

Tumor Markers	Age	ESR	CRP
CA19-9	0.1549**	0.0936	0.0209
CA125	0.0030	0.0822	0.1984
CEA	0.2405***	−0.0314	−0.0740
CA153	0.0824	0.0705	−0.0121
CYFRA21-1	0.1475*	−0.0774	−0.1023

Notes: *p<0.05; **p<0.01; ***p<0.001.

Abbreviations: CTDs, connective tissue diseases; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; CYFRA21-1, cytokeratin 19 fragment.

Table 5 Logistic Regression Analysis of the Association of Tumor Markers and CTD-ILD

Tumor Markers	p value	OR	95% CI
CA19-9	0.173	1.034	(0.989, 1.089)
CA125	0.547	1.008	(0.982, 1.037)
CEA	0.056	1.384	(1.006, 1.970)
CA153	0.001	1.159	(1.064, 1.276)
CYFRA21-1	<0.001	2.269	(1.482, 3.619)

Abbreviations: CTD-ILD, connective tissue disease-related interstitial lung disease; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; CYFRA21-1, cytokeratin 19 fragment; OR, odds ratio; CI, confidence interval.

Table 6 AUC, Cut-Off Value, and Sensitivity and Specificity of Tumor Markers Level for Diagnosis of ILDs Using a ROC Curve

Tumor Markers	AUC (95% CI)	Cut-Off Value	Sensitivity, %	Specificity, %
CA19-9	0.626 (0.554, 0.697)	6.75 U/mL	56.6	70.0
CA125	0.556 (0.483, 0.630)	26.6 U/mL	33.1	93.3
CEA	0.680 (0.611, 0.748)	1.79 ng/mL	49.0	86.7
CA153	0.736 (0.672, 0.801)	9.45 U/mL	58.6	86.7
CYFRA21-1	0.718 (0.649, 0.786)	2.13 ng/mL	60.7	85.6
Combination of CA153 and CYFRA21-1	0.776 (0.715, 0.836)	-	75.2	72.2

Abbreviations: ILDs, interstitial lung diseases; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; CYFRA21-1, cytokeratin 19 fragment; AUC, area under the curve; CI, confidence interval.

Figure 2 The predictive potential of tumor marker levels for the presence of ILDs in patients with CTDs, including CA19-9 (A), CA125 (B), CEA (C), CA153 (D), CYFRA21-1 (E) and the combination of CA153 and CYFRA21-1 (F).