Role of Notch signaling pathway in gastric cancer: A meta-analysis of the literature

Table 1 Characteristics of studies included in the meta-analysis

Ref.	Country	Ethnicity	Study design	Detected target	No. of cases detected for Notch1	No. of controls detected for Notch1	No. of cases detected for Hes1	No. of controls detected for Hes1	No. of cases detected for Jagged1	No. of controls detected for Jagged1
Gou et al[7]	China	Asians	HCC	Notch1	108	NC	-	-	-	-
Huang et al[8]	China	Asians	HCC	Notch1	68	28	-	-	-	-
Kang et al[9]	South Korea	Asians	HCC	Notch1, Notch3, Jagged1, Jagged2, Hes1	103	NC	103	NC	103	NC
Li et al[10]	China	Asians	HCC	Notch1	168	27	-	-	-	-
Liu et al[11]	China	Asians	HCC	Notch1	317	NC	-	-	-	-
Piazzi et al[12]	Italy	Caucasians	HCC	DLL1	-	-	-	-	-	-
Sun et al[13]	China	Asians	HCC	Notch1, Notch2, Hes1	74	10	74	10	-	-
Wang et al[14]	China	Asians	HCC	Notch1, Hes1, NICD	72	16	72	16	-	-
Yang et al[15]	China	Asians	HCC	Notch1	135	27	-	-	-	-
Yang et al[16]	China	Asians	HCC	Notch1, Jagged1, DLL1	63	63	-	-	63	63
Yeh et al[17]	Taiwan, China	Asians	HCC	Notch1, Jagged1	90	NC	-	-	96	NC
Zhang et al[18]	China	Asians	HCC	Notch1, DLL4	45	25	-	-	-	-
Zhang et al[19]	China	Asians	HCC	Notch1	54	54	-	-	-	-
Zhou et al[20]	China	Asians	HCC	Jagged1, Notch1	60	NC	-	-	60	20
Ishigami et al[21]	Japan	Asians	HCC	DLL4	-	-	-	-	-	-

HCC: Hospital-based case-control; NC: No control; DLL: Delta-like; NICD: Intracellular domain of Notch.

Table 2 Meta-analysis of Notch1 and gastric cancer

Stratification of gastric cancer	No. of participants	OR (95%CI)	Statistical method	P value	Ref.
Gender:	1040	1.21 (0.92-1.59)	Fixed	0.18	9[8-11,15,17-20]
Male vs female
Age (yr):	607	1.36 (0.96-1.91)	Fixed	0.08	4[8,10,11,19]
≤ 60 vs > 60
Location:	589	0.62 (0.43-0.91)	Fixed	0.01a	5[8,11,17,19,20]
Cardia vs noncardia
Tumor size:	634	0.68 (0.49-0.94)	Fixed	0.02a	5[8,11,15,19,20]
≤ 5 cm vs > 5 cm
Lauren's classification:	680	1.45 (1.03-2.03)	Fixed	0.03a	5[9,11,13,15,17]
Intestinal vs diffuse
Histological differentiation:	1220	1.42 (0.85-2.37)	Random	0.17	11[7-11,14,15,17-20]
Well/moderate vs poor/undifferentiated
Lymphovascular invasion:	258	0.49 (0.28-0.87)	Fixed	0.01a	2[10,17]
Negative vs positive
T stage:	453	0.71 (0.24-2.09)	Random	0.54	5[7,10,14,18,20]
T1-2 vs T3-4
N stage:	1220	1.07 (0.57-2.00)	Random	0.83	11[7-11,14,15,17-20]
N0 vs N1-3
Distal metastasis:	285	0.33 (0.14-0.78)	Fixed	0.01a	3[10,14,18]
Negative vs positive
TNM stage:	567	0.91 (0.53-1.57)	Random	0.74	7[8,9,14,15,17-19]
Stages I-II vs III-IV

^aP < 0.05. TNM: Tumor node metastasis.

Table 3 Meta-analysis of other components of Notch signaling pathway and gastric cancer

Stratification of gastric cancer	Notch2		Notch3		Jagged1		Jagged2		DLL4		Hes1
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Tumor tissue vs normal tissue	292.00 (23.75-3589.39)	< 0.01a	-	-	0.94 (0.00-254.96)	0.98	-	-	3.84 (2.52-5.83)	< 0.01a	14.31 (4.11-49.87)	< 0.01a
Gender:	-	-	1.01 (0.46-2.26)	0.97	1.26 (0.36-4.39)	0.36	2.90 (0.76-11.02)	0.12	1.03 (0.57-1.86)	0.93	1.05 (0.47-2.35)	0.90
Male vs female
Age (yr):	-	-	0.75 (0.30-1.88)	0.54	1.19 (0.48-2.94)	0.70	0.17 (0.02-1.40)	0.10	0.52 (0.13-2.16)	0.37	1.13 (0.45-2.81)	0.80
≤ 55 vs > 55
Location:	-	-	-	-	0.63 (0.26-1.50)	0.30	-	-	-	-	-	-
Cardia vs noncardia
Lauren's classification:	0.60 (0.02-15.19)	0.76	2.61 (1.17-5.84)	0.02a	2.02 (1.11-3.69)	0.02a	3.97 (1.17-13.46)	0.03a	-	-	1.71 (0.88-3.30)	0.11
Intestinal vs diffuse
Histological differentiation:	-	-	2.04 (0.89-4.67)	0.09	2.18 (1.23-3.86)	< 0.0a	1.36 (0.44-4.18)	0.60	0.89 (0.52-1.54)	0.69	1.78 (0.95-3.34)	0.07
Well/moderate vs poor/undifferentiated
T stage:	-	-	2.40 (0.73-7.92)	0.15	0.50 (0.03-8.54)	0.63	3.70 (1.05-13.08)	0.04a (T1 vs T2-4)	0.29 (0.16-0.54)	< 0.01a	1.72 (0.49-6.00)	0.39 (T1 vs T2-4)
T1-2 vs T3-4
N stage:	-	-	1.84 (0.71-4.75)	0.21	0.82 (0.44-1.50)	0.51	0.91 (0.23- 3.55)	0.89	0.12 (0.06-0.23)	< 0.01a	0.39 (0.04-4.38)	0.45
N0 vs N1-3
Distal metastasis:	-	-	-	-	-	-	-	-	0.55 (0.10-3.00)	0.49	1.76 (0.36-8.51)	0.48
Negative vs positive
TNM stage:	-	-	1.19 (0.54-2.63)	0.67	0.78 (0.42-1.42)	0.41	1.32 (0.44-3.98)	0.62	0.15 (0.03-0.80)	0.03a	0.70 (0.15-3.36)	0.66
Stages I-II vs III-IV

^aP < 0.05. DLL: Delta-like; TNM: Tumor node metastasis.