Prediction of lymph node metastasis in early gastric signet-ring cell carcinoma: A real-world retrospective cohort study

Table 1 Clinical characteristics in patients with early gastric cancer

	SRCC	NSRC	P value
	n = 249, n (%)	n = 1673, n (%)
Age (yr)	53.14 ± 10.03	57.01 ± 11.78	< 0.001
≤ 65	161 (64.66)	634 (37.90)
> 65	88 (35.34)	1039 (62.10)
Gender			< 0.001
Male	133 (53.41)	1238 (74.00)
Female	116 (46.59)	435 (26.00)
Location			< 0.001
Cardia	11 (4.42)	235 (14.05)
Fundus	5 (2.01)	143 (8.55)
Body	43 (17.27)	296 (17.69)
Antrum	129 (51.81)	641 (38.31)
Angle	61 (24.50)	358 (21.40)
Macroscopic type			0.105
Protruded (0-I)	3 (1.20)	27 (1.61)
Elevated (0-IIa)	11 (4.42)	128 (7.65)
Flat (0-IIb)	52 (20.88)	353 (21.10)
Depressed (0-IIc)	178 (71.49)	1076 (64.32)
Excavated (0-III)	5 (2.01)	89 (5.32)
Tumor size (cm)	2.14 ± 1.43	1.89 ± 1.22	0.001
≤ 2	139 (55.82)	1124 (67.18)
> 2	110 (44.18)	549 (32.82)
Ulceration			0.027
UL (-)	175 (70.28)	1046 (62.52)
UL (+)	74 (29.72)	627 (37.48)
Depth of invasion			0.001
M	149 (59.84)	808 (48.30)
SM	100 (40.16)	865 (51.70)
LVI			1
Absence	231 (92.77)	1555 (92.95)
Presence	18 (7.23)	118 (7.05)
Perineural invasion			0.041
Absence	242 (97.19)	1658 (99.10)
Presence	7 (2.81)	15 (0.90)
LNM			< 0.001
Absence	187 (75.10)	1457 (87.09)
Presence	62 (24.90)	216 (12.91)

SRCC: Signet-ring cell carcinoma; NSRC: Non-signet ring cell carcinoma; LVI: Lymphovascular invasion; LNM: Lymph node metastasis; M: Mucosal; SM: Submucosal; UL (-): Ulcer or ulcer scar is absent; UL (+): Ulcer or ulcer scar is present.

Table 2 Logistic regression analysis of the risk factors of lymph node metastasis in early gastric cancer

	LNM		Univariate	Multivariate analysis
	Present	Absent	P value	OR	95%CI	P value
Total	278	1644
Age			0.015
≤ 65	135	660
> 65	143	984
Gender			< 0.001
Male	160	1211		1
Female	118	433		1.912	1.392-2.626	< 0.001
Location			0.001
Cardia	17	229
Fundus	9	139
Body	45	294
Antrum	141	629
Angle	66	353
Macroscopic type			0.008
Protruded (0-I)	9	21
Elevated (0-IIa)	16	123
Flat (0-IIb)	37	368
Depressed (0-IIc)	201	1053
Excavated (0-III)	15	79
Tumor size (cm)			< 0.001
≤ 2	134	1129		1
> 2	144	515		1.875	1.260-2.417	0.001
Ulceration			< 0.001
UL (-)	134	1087		1
UL (+)	144	557		1.695	1.246-2.306	0.001
Depth of invasion			< 0.001
M	54	903		1
SM	224	741		3.34	2.156-5.174	< 0.001
LVI			< 0.001
Absence	199	1587		1
Presence	79	57		6.682	4.358-10.245	< 0.001
Perineural invasion			< 0.001
Absence	262	1638
Presence	16	6
Histological type
Pure SRCC	8	87	< 0.001	1		< 0.001
NSRC	216	1457		2.619	1.454-3.598	0.894
Mixed SRCC	54	100		4.595	2.654-6.954	< 0.001

SRCC: Signet-ring cell carcinoma; NSRC: Non-signet ring cell carcinoma; M: Mucosal; SM: Submucosal; LVI: Lymphovascular invasion; LNM: Lymph node metastasis; UL (-): Ulcer or ulcer scar is absent; UL (+): Ulcer or ulcer scar is present.

Table 3 The Classification of the artificial neural network model and logistic regression model

Models	Predicted results	Pathological diagnosis
		+	-	Percent correct
LR	+	77	55	58.3%
	-	201	1589	88.8%
	Percent correct	27.7%	96.7%	86.7%
ANN	+	54	2	96.4%
	-	224	1642	88.0%
	Percent correct	19.4%	99.9%	88.2%

LR: Logistic regression; ANN: Artificial neural network.

Table 4 Comparison of artificial neural network model and logistic regression model for predicting lymph node metastasis

Diagnostic Index	LR model, (%, 95%CI)	ANN model (%, 95%CI)	P value
Sensitivity	58.3% (48.6-67.1%)	96.4% (87.8-99.9%)	0.034
Specificity	88.8% (87.2-90.4%)	88.0% (86.4-89.6%)	< 0.001
PPV	27.7% (22.3-33.9%)	19.4% (14.9-25.2%)	< 0.001
NPV	96.7% (95.6-97.5%)	99.9% (99.6-1.000%)	0.202
Accuracy	86.7% (85.1-88.2%)	88.2% (86.8-89.8%)	< 0.001
AUC	0.797 (0.776-0.818)	0.878 (0.862-0.893)	< 0.001

PPV: Positive predictive value; NPV: Negative predictive value; AUC: Area under the curve.

Table 5 Clinical characteristics in patients with pure signet-ring cell carcinoma and mixed signet-ring cell carcinoma

Variable	Pure SRCC	Mixed SRCC	P value
	n = 95, n (%)	n = 154, n (%)
Age (yr)			0.037
≤ 65	70 (73.68)	91 (59.09)
> 65	25 (26.32)	63 (40.91)
Gender			0.131
Male	46 (48.42)	87 (56.49)
Female	49 (51.58)	67 (43.51)
Location			0.255
Cardia	4 (4.21)	7 (4.55)
Fundus	2 (2.11)	3 (1.95)
Body	13 (13.68)	30 (19.48)
Antrum	51 (53.68)	78 (50.65)
Angle	25 (26.32)	36 (23.38)
Macroscopic type			0.152
Protruded (0-I)	1 (1.05)	2 (1.30)
Elevated (0-IIa)	5 (5.26)	6 (3.90)
Flat (0-IIb)	23 (24.21)	29 (18.83)
Depressed (0-IIc)	65 (68.42)	113 (73.38)
Excavated (0-III)	1 (1.05)	4 (2.60)
Tumor size (cm)			0.126
≤ 2	60 (63.16)	79 (51.30)
> 2	35 (36.84)	75 (48.70)
Ulceration			0.051
UL (-)	75 (78.95)	100 (64.94)
UL (+)	20 (21.05)	54 (35.06)
Depth of invasion			< 0.001
M	71 (74.74)	78 (50.65)
SM	24 (25.26)	76 (49.35)
LVI			0.002
Absence	95 (100.00)	136 (88.31)
Presence	0 (0.00)	18 (11.69)
Perineural invasion			0.420
Absence	94 (98.95)	148 (96.10)
Presence	1 (1.05)	6 (3.90)
LNM			< 0.001
Absence	87 (91.58)	100 (64.94)
Presence	8 (8.42)	54 (35.06)

SRCC: Signet-ring cell carcinoma; M: Mucosal; SM: Submucosal; LNM: Lymph node metastasis; LVI: Lymphovascular invasion; UL (-): Ulcer or ulcer scar is absent; UL (+): Ulcer or ulcer scar is present.

Table 6 Logistic regression analysis of the risk factors of lymph node metastasis in signet-ring cell carcinoma

	LNM		Univariate	Multivariate analysis
	Present	Absent	P value	OR	95%CI	P value
Total	62	187
Age			0.617
≤ 65	41	120
> 65	21	67
Gender			0.639
Male	32	101
Female	30	86
Location			0.544
Cardia	2	9
Fundus	1	4
Body	10	33
Antrum	33	96
Angle	16	45
Macroscopic type			0.209
Protruded (0-I)	0	3
Elevated (0-IIa)	1	10
Flat (0-IIb)	13	39
Depressed (0-IIc)	46	132
Excavated (0-III)	2	3
Tumor size (cm)			0.351
≤ 2	30	109
> 2	32	78
Ulceration			0.06
UL (-)	37	128
UL (+)	25	46
Depth of invasion			< 0.001
M	20	129		1
SM	42	58		2.615	1.282-5.334	0.008
LVI			< 0.001
Absence	46	185		1
Presence	16	2		14.903	3.143-70.680	0.001
Perineural invasion			0.146
Absence	58	184
Presence	4	3
Histological type			< 0.001
Pure SRCC	8	87		1
Mixed SRCC	54	100		1.982	0.923-4.237	0.043

SRCC: Signet-ring cell carcinoma; M: Mucosal; SM: Submucosal; LNM: Lymph node metastasis; LVI: Lymphovascular invasion; UL (-): Ulcer or ulcer scar is absent; UL (+): Ulcer or ulcer scar is present.

Table 7 Logistic regression analysis of the risk factors of lymph node metastasis in signet-ring cell carcinoma limited in mucosal

	LNM		Univariate	Multivariate analysis
	Present	Absent	P value	OR	95%CI	P value
Total	20	129
Age			0.195
≤ 65	10	80
> 65	10	49
Gender			0.306
Male	9	77
Female	11	52
Tumor size (cm)			0.123
≤ 2	8	78
> 2	12	51
Macroscopic type			0.209
Protruded (0-I)	0	2
Elevated (0-IIa)	0	7
Flat (0-IIb)	4	27
Depressed (0-IIc)	15	91
Excavated (0-III)	1	2
LVI			0.016
Absence	18	129
Presence	2	0
Perineural invasion			-
Absence	20	129
Presence	0	0
Location			0.688
Cardia	1	6
Fundus	0	3
Body	3	23
Antrum	11	66
Angle	5	31
Ulceration			1
UL (-)	15	101
UL (+)	3	28
Histological type			0.01
Pure SRCC	3	66		1
Mixed SRCC	17	63		4.557	1.235-16.820	0.023

SRCC: Signet-ring cell carcinoma; LNM: Lymph node metastasis; LVI: Lymphovascular invasion; UL (-): Ulcer or ulcer scar is absent; UL (+): Ulcer or ulcer scar is present.

Table 8 Logistic regression analysis of the risk factors of lymph node metastasis in pure and mixed signet-ring cell carcinoma

	LNM				Univariate		Multivariate analysis
	Present		Absent		P value		OR, 95%CI, P value
	Pure	Mixed	Pure	Mixed	Pure	Mixed	Pure	Mixed
Total	8	54	87	100
Age					1	1
≤ 65	7	33	58	63
> 65	1	21	29	37
Gender					1	0.377
Male	3	29	39	62
Female	5	25	48	38
Location					0.706	0.412
Cardia	0	2	4	5
Fundus	0	1	2	2
Body	1	9	12	21
Antrum	5	28	46	50
Angle	2	14	23	22
Macroscopic type					0.788	0.314
Protruded (0-I)	0	0	1	2
Elevated (0-IIa)	0	1	5	5
Flat (0-IIb)	3	10	20	19
Depressed (0-IIc)	4	42	61	71
Excavated (0-III)	1	1	0	3
Tumor size (cm)					0.014	0.751
≤ 2	4	26	56	53			1
> 2	4	28	31	47			5.422 (1.095-26.856), 0.038
Ulceration					1	0.189
UL (-)	6	31	69	69
UL (+)	2	23	18	31
Depth of invasion					0.045	0.004
M	3	17	70	59				1
SM	5	37	17	41				2.395 (0.891-4.998), 0.054
LVI					-	< 0.001
Absence	8	38	87	98				1
Presence	0	16	0	2				16.173 (4.085-76.619), 0.001
Perineural invasion					1	0.376
Absence	8	50	86	98
Presence	0	4	1	2
Mixed component						0.458
Differentiated	-	1	-	7
Undifferentiated	-	30	-	58
Mixed	-	23	-	35

M: Mucosal; SM: Submucosal; LNM: Lymph node metastasis; LVI: Lymphovascular invasion; UL (-): Ulcer or ulcer scar is absent; UL (+): Ulcer or ulcer scar is present.

Table 9 Lymph node metastasis in early gastric signet-ring cell carcinoma according to therapeutic criteria

	Meet expanded ESD indication			Beyond expanded ESD indication			P value
	Total	LNM (+)	LNM (-)	Total	LNM (+)	LNM (-)
p-SRCC	41	1	40	54	7	47	0.132
m-SRCC	31	5	26	123	45	78	0.048
Total	72	6	66	177	52	125	0.001

ESD: Endoscopic submucosal dissection; p-SRCC: Pure signet-ring cell carcinoma; m-SRCC: Mixed signet-ring cell carcinoma; LNM: Lymph node metastasis.