Clinical Value of Combined Detection of Serum sTim-3 and Pepsinogen for Gastric Cancer Diagnosis

Figures & data

Figure 1 (A) PGI levels in controls and BGD and first-diagnosis GC patients; (B) PGII levels in controls and BGD and first-diagnosis GC patients; (C) PGI/PGII ratio in controls and BGD and first-diagnosis GC patients; (D) sTim-3 levels in controls and BGD and first-diagnosis GC patients; (E) sTim-3 levels in first-diagnosis GC patients (stage I, stage II, stage III, and stage IV); (F) sTim-3 levels in controls, recurrence group after GC surgery, and no recurrence group after GC surgery. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Table 1 Serum Indices of Control, BGD, First-Diagnosis GC, and Post-Operative GC Groups

Index		Control (n=73)	BGD (n=81)	First-Diagnosis GC (n=123)	Post-Operative (n=26)
					No Recurrence (n=17)	Recurrence (n=9)
Sex	Male	34 (46.6%)	47 (58.0%)	78 (63.4%)	10 (58.8%)	6 (66.6%)
	Female	39 (53.4%)	34 (42.0%)	45 (36.6%)	7 (41.20%)	3 (33.4%)
Age (years)		40.06 ± 10.31	60.83 ± 12.16	66.78 ± 8.81	63.50 ± 8.09	70.20 ± 10.03
sTim-3 (ng/mL)		9.22 ± 3.40	16.50 ± 9.76^a	20.41 ± 9.55^ab	11.95 ± 5.16^bc	33.56 ± 4.91^abc
PGI (ng/mL)		146.89 ± 47.68	123.93 ± 79.16^a	145.34 ± 119.31	46.25 ± 39.81^abc	52.67 ± 43.69^abc
PGII (ng/mL)		11.94 ± 6.24	18.39 ± 14.94^a	22.94 ± 13.66^a	6.02 ± 5.38^abc	5.61 ± 3.78^abc
PGI/PGII ratio		13.91 ± 4.49	9.25 ± 4.43^a	9.24 ± 5.43^a	6.12 ± 3.55^abc	9.73 ± 4.74^a

Notes: Quantitative data are expressed as the mean ± SD, and the difference was analyzed by ANOVA followed by Tukey’s multiple comparison test. ^aP < 0.05 compared with control; ^bP < 0.05 compared with BGD; ^cP < 0.05 compared with GC.

Abbreviations: PG, pepsinogen; BGD, benign gastric disease; GC, gastric cancer.

Table 2 Positive Detection Rates of PGI, PGII, and sTim-3 Levels and the PGI/PGII Ratio in the Control, BGD, and First-Diagnosis GC Groups

Index	Number of Positive Control Detections (n=73)	Number of Positive BGD Detections (n=81)	Number of Positive First-Diagnosis GC Detections (n=123)
PGI > 210 ng/mL or PGII > 23 ng/mL	11 (15.01%)	27 (33.33%)	45 (36.59%)
PGI < 70 ng/mL and PGI/PGII < 6	0 (0%)	10 (12.35%)	23 (18.70%)
PG abnormal	11 (15.01%)	37 (45.68%)	68 (55.28%)
sTim-3 > 16.03 ng/mL	2 (2.74%)	43 (53.09%)	76 (61.79%)
PG abnormal or sTim-3 > 16.03 ng/mL	13 (17.80%)	52 (64.20%)	96 (78.05%)
PG abnormal and sTim-3 > 16.03 ng/mL	0 (0%)	16 (19.75%)	40 (32.52%)

Notes: Positive PGI, PGII, PGI/PGII were determined in accordance with the kit’s cut-off values; positive sTim-3 are expressed as the mean + 2 SD.

Abbreviations: PG, pepsinogen; BGD, benign gastric disease; GC, gastric cancer.

Table 3 Independent Diagnostic Value of Serum Markers in BGD and First-Diagnosis GC

		Cut-Off	Sensitivity	Specificity	AUC	95% CI	P-value
Control vs BGD	sTim-3 (ng/mL)	13.41	64.20%	91.78%	0.8322	0.7686 to 0.8959	<0.0001
	PGI (ng/mL)	107.00	50.62%	84.93%	0.6411	0.5522 to 0.7301	0.0025
	PGII (ng/mL)	16.28	41.98%	84.93%	0.6023	0.5122 to 0.6924	0.0286
	PGI/PGII	9.55	71.25%	84.93%	0.8009	0.7277 to 0.8742	<0.0001
Control vs First-diagnosis GC	sTim-3 (ng/mL)	14.30	73.98%	95.89%	0.9093	0.8693 to 0.9493	<0.0001
	PGI (ng/mL)	88.80	47.06%	93.15%	0.6018	0.5211 to 0.6819	0.0180
	PGII (ng/mL)	17.51	41.18%	89.04%	0.6068	0.5278 to 0.6858	0.0131
	PGI/PGII	12.11	77.12%	67.12%	0.7773	0.7122 to 0.8424	<0.0001
BGD vs First-diagnosis GC	sTim-3 (ng/mL)	19.46	47.15%	85.19%	0.6743	0.5999 to 0.7488	<0.0001
	PGI (ng/mL)	209.6	27.73%	87.65%	0.5122	0.4321 to 0.5923	0.7700
	PGII (ng/mL)	19.46	33.61%	65.43%	0.5063	0.4238 to 0.5888	0.8793
	PGI/PGII	9.51	41.53%	71.25%	0.5410	0.4592 to 0.6229	0.3274

Notes: The diagnostic value of variables was analyzed by ROC analysis. Youden index was used to determine the optimal cut-off value (cut-off). P < 0.05 was considered statistically significant.

Abbreviations: AUC, area under the curve; CI, confidence intervals; PG, pepsinogen; BGD, benign gastric disease; GC, gastric cancer.

Figure 2 Independent diagnostic value of serum sTim-3, PGI, and PGII levels and the PGI/PGII ratio in BGD and first-diagnosis GC analyzed by ROC. (A) ROC curves of serum marker levels between the controls and BGD patients; (B) ROC curves of serum marker levels between the controls and first-diagnosis GC patients; (C) ROC curves of serum marker levels between BGD and first-diagnosis GC patients.

Table 4 Diagnostic Value of Serum Marker Combinations in BGD and First-Diagnosis GC

		Sensitivity	Specificity	AUC	95% CI	P-value
Control vs BGD	PGI + PGI/PGII	67.90%	89.04%	0.8031	0.7300 to 0.8763	<0.0001
	sTim-3 + PGI	90.12%	64.38%	0.8537	0.7952 to 0.9123	<0.0001
	sTim-3 + PGI/PGII	79.01%	87.67%	0.8879	0.8333 to 0.9424	<0.0001
	sTim-3 + PGI + PGI/PGII	79.01%	87.67%	0.8953	0.8425 to 0.9481	<0.0001
Control vs First-diagnosis GC	PGII + PGI/PGII	82.20%	67.12%	0.7958	0.7315 to 0.8601	<0.0001
	sTim-3 + PGII	77.97%	95.89%	0.9135	0.8739 to 0.9535	<0.0001
	sTim-3 + PGI/PGII	86.44%	91.78%	0.9330	0.8977 to 0.9683	<0.0001
	sTim-3 + PGII + PGI/PGII	89.83%	89.04%	0.9438	0.9129 to 0.9746	<0.0001
BGD vs First-diagnosis GC	PGII + PGI/PGII	56.78%	51.85%	0.5161	0.4343 to 0.6978	<0.0001
	sTim-3 + PGII	50.00%	81.48%	0.6775	0.6026 to 0.7525	<0.0001
	sTim-3 + PGI/PGII	56.78%	72.84%	0.6735	0.5982 to 0.7487	0.7005
	sTim-3 + PGII + PGI/PGII	52.54%	79.00%	0.6775	0.6026 to 0.7525	<0.0001

Notes: The diagnostic value of variables was analyzed by ROC analysis. Youden index was used to determine the optimal cut-off value (cut-off). P < 0.05 was considered statistically significant.

Abbreviations: AUC, area under the curve; CI, confidence interval; PG, pepsinogen; BGD, benign gastric disease; GC, gastric cancer.

Figure 3 Independent diagnostic value of serum sTim-3, PGI, and PGII levels and the PGI/PGII ratio in BGD and first-diagnosis GC patients was analyzed by ROC analysis. (A) ROC curves of serum marker levels between the controls and BGD patients; (B) ROC curves of serum marker levels between the control and first-diagnosis GC patients; (C) ROC curves of serum marker levels between BGD and first-diagnosis GC patients.

Table 5 Positive Detection Rate of the New Cut-Off Value of Combined Detection in BGD and GC

Group	Index	Number of Positive Control Detections (n=73)	Number of Positive BGD Detections (n=81)	Number of Positive First-Diagnosis GC Detections (n=123)
BGD diagnosis	PGI/PGII < 9.55 and sTim-3 > 13.41 ng/mL	0 (0%)	37 (45.68%)	50 (40.65%)
	PGI/PGII < 9.55 or sTim-3 > 13.41 ng/mL	16 (21.92%)	68 (83.95%)	113 (91.87%)
GC diagnosis	PGI/PGII < 12.11 and sTim-3 > 14.30 ng/mL	0 (0%)	29 (35.80%)	67 (54.47%)
	PGI/PGII > 12.11 or sTim-3 > 14.30 ng/mL	19 (26.03%)	70 (86.42%)	115 (93.59%)
Distinguish BGD from GC	PGII>19.46 ng/mL or sTm-3 > 19.46ng/mL	0 (0%)	3 (3.70%)	25 (20.33%)
	PGII>19.46 ng/mL or sTm-3 > 19.46ng/mL	12 (16.44%)	36 (44.44%)	82 (66.67%)

Abbreviations: PG, pepsinogen; BGD, benign gastric disease; GC, gastric cancer. The Youden index was used to determine the optimal cut-off value (cut-off).