Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

Figures & data

Table I. Patient and tumor characteristics.

Cohort (no)	ESCC (129)	AC (66)
Sex, no. (%)
Male	85 (66)	55 (83)
Female	44 (34)	11 (17)
Age, year
Median (range)	63 (36–81)	64 (32–86)
Tumor length (endoscopy)^a	n = 90	n = 43
Median (range)	50 (10–150)	50 (10–100)
Clinical T stage (cT), no. (%)
TX	8 (6)	24 (36)
T1	2 (2)
T2	32 (25)	20 (30)
T3	75 (58)	19 (29)
T4	12 (9)	3 (5)
Clinical N-stage (cN), no. (%)
NX	5 (4)	11 (17)
N0	37 (29)	21 (32)
N1	80 (62)	34 (51)
N2	7 (5)
Clinical M stage (cM), no. (%)
MX	7 (5)	10 (15)
M0	117 (91)	55 (83)
M1-1a	5 (4)	1 (2)
Pathological response, no. (%)^b	n = 68	n = 44
CR	28 (41)
Non-CR	40 (59)	44 (100)
Status CT, no. (%)
Complete response	24 (19)	9 (14)
Regression	53 (41)	28 (41)
Stable disease	32 (25)	18 (27)
Progression	9 (7)	5 (8)
Recurrence of disease	4 (3)	1 (2)
Unknown	7 (5)	5 (8)

^aESCC: N = 90, EAC: N = 43; ^bESCC: N = 68, EAC: N = 44.

Table II. Uni- and multivariate analyses.

	ESCC		EAC
	HR (95% CI)	P	HR (95% CI)	P
Univariate analyses
Risk of disease-specific death
Age (> median age vs. ≤ median age)	1.59 (0.94–2.69)	0.081	1.01 (0.46–2.19)	0.984
Gender (male vs. female)	1.72 (0.96–3.10)	0.070	0.93 (0.32–2.69)	0.889
Tumor classification (T3–4 vs. T1–2)	1.99 (1.03–3.86)	0.041	1.87 (0.71–4.92)	0.204
Nodal classification (N1 vs. N0)	2.16 (1.09–4.28)	0.028	1.54 (0.63–3.75)	0.339
miR-21 (High exp. vs. low/interm. exp.)*	1.76 (1.05–2.97)	0.033	3.37 (1.41–8.05)	0.006
Risk of death from any cause
Age (> median age vs. ≤ median age)	1.40 (0.89–2.22)	0.145	1.17 (0.60–2.30)	0.645
Gender (male vs. female)	1.52 (0.92–2.52)	0.101	0.81 (0.33–1.95)	0.635
Tumor classification (T3–4 vs. T1–2)	1.78 (1.01–3.16)	0.048	2.50 (1.01–6.22)	0.048
Nodal classification (N1 vs. N0)	1.62 (0.93–2.83)	0.089	2.01 (0.85–4.73)	0.110
miR-21 (High exp. vs. low/interm. exp.)*	1.50 (0.95–2.39)	0.084	1.96 (0.98–3.94)	0.058
Multivariate analyses
Risk of disease-specific death
Age (> median age vs. ≤ median age)	1.30 (0.75–2.27)	0.350
Gender (male vs. female)	1.54 (0.83–2.88)	0.173
Tumor classification (T3–4 vs. T1–2)	1.44 (0.69–2.99)	0.328	1.91 (0.71–5.14)	0.199
Nodal classification (N1 vs. N0)	1.61 (0.73–3.57)	0.241	1.07 (0.31–3.64)	0.915
miR-21 (High exp. vs. low/interm. exp.)*	1.50 (0.86–2.62)	0.158	3.52 (1.06–11.69)	0.040
Risk of death from any cause
Age (> median age vs. ≤ median age)	1.31 (0.80–2.13)	0.284
Gender (male vs. female)	1.29 (0.76–2.20)	0.350
Tumour classification (T3–4 vs. T1–2)	1.48 (0.79–2.80)	0.224	2.40 (0.96–6.01)	0.060
Nodal classification (N1 vs. N0)	1.27 (0.66–2.45)	0.471	1.73 (0.54–5.52)	0.353
miR-21 (High exp. vs. low/interm. exp.)*	1.37 (0.83–2.26)	0.211	1.84 (0.70–4.79)	0.215

^aFor ESCC, uni- and multivariate analyses were performed with miR-21 expression divided by tertiles (high exp. vs. low/interm. exp.); ^bFor EAC, uni- and multivariate analyses were performed with miR-21 expression divided by median (high exp. vs. low exp.).

Figure 1. Kaplan-Meier estimates of miR-21 expression on survival in patients with ESCC. (A) DSS (divided by median expression), (B) OS (divided by median expression), (C) DSS (divided by tertiles – high exp. vs. low/interm. exp.) and (D) OS (divided by tertiles – high exp. vs. low/interm. exp.).

Figure 2. Kaplan-Meier estimates of miR-21 expression on survival in patients with EAC. (A) DSS (divided by median expression), (B) OS (divided by median expression), (C) DSS (divided by tertiles – high exp. vs. low/interm. exp.) and (D) OS (divided by tertiles – high exp. vs. low/interm. exp.).

Figure 3. Forest plots evaluating the association between (A) miR-21 expression and prognosis in ESCC and (B) miR-375 expression and prognosis in ESCC. The squares represent study weights (inversely proportional to the standard error of the respective HRs) and are centred on the HR. 95% CIs are represented with whiskers. The dotted lines indicate the overall hazard ratio estimates.