Clinical significance of signet ring cells in surgical esophageal and esophagogastric junction adenocarcinoma: A systematic review and meta-analysis

Table 1 Basic characteristics of included studies

Author	Year	Country	Sample size	Location	TNM	SRC ratio	Endpoint	NOS
Chirieac et al[11]	2005	United States (ACC: 1985-2003)	193	Esophageal + EGJ	I-IV	> 0%	OS	7
Chirieac et al[11]	2005	United States (ACC: 1985-2003)	219	Esophageal + EGJ	I-IV	> 0%	OS	7
Yoon et al[12]	2010	United States (MCTR)	796	Esophageal + EGJ	NR	> 0%	OS, DSS, DFS	6
Yendamuri et al[13]	2013	United States (SEER)	11825	Esophageal	I-IV	> 0%	OS,	7
Nafteux et al[14]	2014	Belgium	779	Esophageal + EGJ	I-IV	1%-50%, > 50%	DSS	7
Patel et al[15]	2014	United States (ACC: 2000-2012)	723	Esophageal + EGJ	II-IV	> 0%	OS, DFS	7
Chen et al [16]	2017	China	671	Esophageal	I-III	1%-50%, > 50%	OS	8
Van Hootegem et al[17]	2019	Australia	298	Esophageal + EGJ	NR	> 0%	OS, DFS	7
Van Hootegem et al[17]	2019	Australia	391	Esophageal + EGJ	NR	> 0%	OS, DFS	7
Corsini et al[18]	2020	United States (ACC: 2006-2018)	819	Esophageal	NR	1%-10%, 11%-49%, ≥ 50%	OS	8
Sathe et al[19]	2020	United States (NCD: 2004-2015)	14224	Esophageal + EGJ	I-III	NR	OS	7
Solomon et al[20]	2021	Israel	163	Esophageal + EGJ	I-III	> 0%	OS	6

SRC: Signet ring cell; NOS: Newcastle-Ottawa Scale; EGJ: Esophagogastric junction; Surg: Surgery; nCT: Neoadjuvant chemotherapy; OS: Overall survival; DSS: Disease-specific survival; DFS: Disease-free survival; SEER: Surveillance, Epidemiology, and End Results; R: Recurrence; ACC: Anderson Cancer Center; MCTR: Mayo Clinic Tumor Registry; RTCT: Response to chemotherapy; NCD: National Cancer Database; DS: Downstaging; TNM: Tumor-node-metastasis; NR: Not reported.

Table 2 Association between signet-ring cells and clinicopathological characteristics

Study	Sex (male)	Smoking	Family history	Tumor location (esophageal)	Lymph node metastasis	TNM stage (III/IV)
Chirieac et al[11] 2005	0.722 (0.254-2.053)	-	-	-	-	0.895 (0.522-1.532)
Chirieac et al[11] 2005	0.730 (0.341-1.564)	-	-	-	-	1.855 (0.997-3.454)
Yoon et al[12] 2010	-	-	-	-	-	-
Yendamuri et al[13] 2013	0.975 (0.783-1.214)	-	-	-	-	1.267 (1.060-1.513)
Nafteux et al[14] 2014	0.882 (0.558-1.395)	-	-	0.636 (0.451-0.896)	-	1.048 (0.702-1.563)
Patel et al[15] 2014	0.518 (0.309-0.867)	-	-	-	1.357 (0.907-2.028)	-
Chen et al[16] 2017	1.461 (0.945-2.258)	0.667 (0.495-0.899)	1.157 (0.762-1.757)	-	-	1.095 (0.811-1.480)
Van Hootegem et al[17] 2019	1.138 (0.662-1.956)	-	-	0.888 (0.649-1.216)	0.929 (0.677-1.275)	-
Corsini et al[18] 2020	0.771 (0.460-1.292)	1.061 (0.923-1.219)	-	-	1.038 (0.888-1.215)	-
Sathe et al[19] 2020	1.164 (0.912-1.485)	-	-	-	-	1.832 (1.542-2.177)
Solomon et al[20] 2021	-	-	-	-	-	-
Overall	0.99, 0.87-1.13, P = 0.917	0.86, 0.55-1.35, P = 0.507	1.157 (0.762-1.757)	0.76, 0.61-0.96, P = 0.022	1.05, 0.92-1.20, P = 0.488	1.30, 1.02-1.65, P = 0.031

TNM: Tumor-node-metastasis.

Table 3 Results of meta-analysis

	No. of studies	HR	95%CI	P value	I2	P value
Overall survival	11[11-13,15-20]	1.36	1.12-1.65	0.002	85.7	< 0.001
Disease-free survival	4[12,15,17]	1.21	0.94-1.57	0.145	63.1	0.043
Disease-specific survival	2[12,14]	1.86	1.55-2.25	< 0.001	0.0	0.323

HR: Hazard ratio; CI: Confidence interval.