hENT1 expression is predictive of gemcitabine outcome in pancreatic cancer: A systematic review

Table 4 Results

Ref.	Median survival all patients (95%CI)	OS		DFS		Main conclusions
		Univariate analysis median (95%CI) or HR (95%CI) P-value	Multivariate analysis HR (95%CI)	Univariate analysis median (95%CI) or HR (95%CI) P-value	Multivariate analysis HR (95%CI)
Spratlin et al[9]	11.01 (6.8-17.5)	(mo):		NR		Pat with detectable hENT1 had sig longer OS compared with pat with low hENT1
		High = 13 (4.2-20.4)
	5.01 (2.8-12.2)	Low = 4 (1.5-6.9)
		P = 0.01
Giovannetti et al[10]	13.3 (10.9-15.7)	(mo):	Low = 5.34 (2.28-12.50)	Palliative (mo):		hENT1 expression was significantly correlated with outcome - pat with high hENT1 had longer OS
		Low = 8.48 (7.01-9.95)		Low = 5.85 (2.75-8.95)
		Inter = 15.74 (13.84-17.63)	Inter = 1.07 (0.46-2.49)	Inter = 10.09 (9.63-10.54)
		High = 25.69 (17.64-33.74)	High = 1	High = 12.68 (2.89-22.47)
		P ≤ 0.001	P < 0.0001	P = 0.02
			2 groups:
		2 groups:	HR = 4.21	Adjuvant (mo):
		Low = 12.42 (8.18-16.66)	P ≤ 0.001	Low = 9.26 (3.86-14.67)
		High = 22.34 (16.34-28.34)		Inter = 12.91 (9.31-16.51)
		P ≤ 0.001		High = 20.43 (13.27-27.60)
				P ≤ 0.01
Farrell et al[12]	NR	(HR):	Low/high = 0.40 (0.22-0.75)	(HR):	Low/high = 0.39 (0.21-0.73)	hENT1 expression was ass with longer OS, DFS in pat receiving gem. hENT1 is a relevant predictive marker for gem outcome
		Low/High = 0.51 (0.29-0.91)		Low/High = 0.57 (0.32-1.001)
		No = 1	No = 1	No = 1	No = 1
		P = 0.02	P = 0.03	P = 0.05	P = 0.003
Maréchal et al[3]	21.9 (3.3-107.4)	(HR):	High = 1	(HR):	High = 1	Pat with high hENT1 had sig longer OS and DFS compared to low hENT1
		High = 1	Low = 3.42 (1.44-8.81)	High = 1	Low = 3.17 (1.43-6.73)
		Low = 3.88 (1.78-8.92)	P = 0.0005	Low = 3.55 (1.65-7.63)	P = 0.0004
		P = 0.0007		P = 0.02
Fujita et al[8]	NR	(mo):	(RR):	(mo):	NR	Low hENT1 ass with shorter OS in gem-group
		High = 45	Low = 2.980 (0.964-10.86)	High = 25
		Low = 16.5		Low = 8
		P = 0.011	P = 0.2 (not sig)	P = 0.11 (not sig)
Maréchal et al[1]	32.0 (26.4-34.3)	(HR):	n = 2222	NR	NR	High hENT1 predicts longer OS in pat treated with adj gem. Absence of gem - hENT1 lacks prognostic value
		High = 0.43 (0.29-0.63)	High = 0.34 (0.22-0.53)
	(GEM-group)	Low/Mod = 1	Low/Mod = 1
		P < 0.0001	P < 0.0001
Kawada et al[2]	NR	Positive vs negative	Positive/negative	NR	NR	DSS tended to be better in the hENT1-neg group but not statistically sig
		P = 0.352	P = 0.503
Morinaga et al[21]	NR	(mo):	Low = 1	(mo):	Low = 1	High hENT1 sig ass with longer OS in pat receiving adj gem after resection
		Low = 11.8 (6.9-16.6)	High = 0.327 (0.128-0.835)	Low = 7.3 (3.6-11.1)	High = 0.558 (0.214-1.452)
		High = 22.2 (11.5-32.9)		High = 9.3 (4.2-14.5)
		P = 0.024	P = 0.019	P = 0.022	P = 0.232
		(HR):		(HR):
		Low = 1		Low = 1
		High = 0.366 (0.148-0.906)		High = 0.362 (0.146-0.898)
		P = 0.030		P = 0.028
Murata et al[22]	24.3	(HR):	Positive = 1	(HR):	Positive = 1	Sig longer OS, RFS in pat with pos hENT1
		Positive = 1	Negative = 3.15 (1.35-7.37)	Positive = 1	Negative = 1.76 (0.85-3.66)
		Negative = 3.04 (1.45-6.37)		Negative = 2.34 (1.22-4-47)
		P = 0.0037	P = 0.008	P = 0.011	P = 0.129
Nakagawa et al[23]	OS: 34.9	(5y-SR %):	High = 1	(5y-SR %):	High = 1	hEN1 expression is predictive of the efficacy of adj gem-based chemotherapy after resection
	DFS: 17.8	High = 38	Low = 3.16 (1.65-6.06)	High = 30	Low = 2.70 (1.52-4.83)
		Low = 13		Low = 17
		P = 0.001	P = 0.001	P = 0.004	P = 0.001

¹From diagnosis/from treatment;

²n = 222 in multivariate analysis. Ass: Associated; pat: Patient; sig: Significant; adj: pos: Positive; op: Operation; HR: Hazard ratio; SR: Survival rate; RFS: Recurrence-free survival.