Correlation of plasma miR-21 and miR-93 with radiotherapy and chemotherapy efficacy and prognosis in patients with esophageal squamous cell carcinoma

Table 1 Diagnostic value of plasma miR-21 and miR-93 for clinicopathological features of esophageal squamous cell carcinoma patients

Pathological feature	AUC	95%CI	SE	Cut-off	Sensitivity (%)	Specificity (%)
MiR-21
T stage	0.819	0.740-0.899	0.041	6.52	80.00	71.43
N stage	0.758	0.666-0.851	0.047	5.90	67.02	79.41
M stage	0.824	0.740-0.908	0.043	6.34	85.71	70.00
Pathological differentiation	0.725	0.637-0.812	0.044	6.20	80.85	59.26
MiR-93
T stage	0.827	0.742-0.911	0.043	4.37	73.33	80.61
N stage	0.815	0.733-0.896	0.041	3.34	74.47	76.47
M stage	0.814	0.722-0.906	0.047	5.36	57.14	97.00

AUC: Area under the receiver operating characteristic curve; CI: Confidence interval.

Table 2 Correlation of plasma miR-21 and miR-93 with clinicopathological features of esophageal squamous cell carcinoma patients (mean ± SD)

Category	n	miR-21	t/F	P value	miR-93	t/F	P-value
Gender			0.867	0.387		0.337	0.737
Male	95	6.06 ± 1.61			3.63 ± 1.75
Female	33	5.77 ± 1.78			3.74 ± 1.14
Age (yr)			0.590	0.556		0.704	0.483
≤ 65	54	5.89 ± 1.61			3.57 ± 1.67
> 65	74	6.06±1.61			3.76 ± 1.38
Smoking history			1.108	0.270		1.013	0.313
Yes	52	5.80 ± 1.47			3.53 ± 1.70
No	76	6.12 ± 1.69			3.80 ± 1.31
History of alcoholism			1.694	0.093		1.286	0.201
Yes	60	5.73 ± 1.54			3.49 ± 1.46
No	68	6.21 ± 1.65			3.83 ± 1.52
T stage			6.078	< 0.001b		6.489	< 0.001d
T2/T3	98	5.57 ± 1.47			3.27 ± 1.31
T4	30	7.37 ± 1.24			5.03 ± 1.27
N stage			4.503	< 0.001b		6.363	< 0.001d
N0	34	5.00 ± 1.28			2.46 ± 1.21
N1	94	6.35 ± 1.57			4.12 ± 1.34
M stage			6.111	< 0.001b		6.315	< 0.001d
M0	100	5.58 ± 1.45			3.30 ± 1.30
M1	28	7.44 ± 1.28			5.06 ± 1.34
Tumor site			0.219	0.804		0.404	0.669
Upper 1/3 of thoracic part	44	6.10 ± 1.46			3.52 ± 1.45
Middle 1/3 of thoracic part	59	5.89 ± 1.69			3.78 ± 1.37
Lower 1/3 of thoracic part	25	6.02 ± 1.70			3.75 ± 1.88
Pathological differentiation			4.379	< 0.001b		1.371	0.172
Medium/high differentiation	47	5.16 ± 1.38			3.09 ± 1.42
Low differentiation	81	6.43 ± 1.61			3.92 ± 1.50
Tumor length (cm)			0.684	0.495		1.219	0.225
≤ 5	30	5.81 ± 1.55			3.39 ± 1.54
> 5	98	6.04 ± 1.63			3.77 ± 1.48

^bP < 0.01 vs control group;

^dP < 0.01 vs esophageal squamous cell carcinoma patients.

Table 3 Predictive value of plasma miR-21 and miR-93 for radiotherapy and chemotherapy efficacy in esophageal squamous cell carcinoma patients

Index	AUC	95%CI	SE	Cut-off	Sensitivity (%)	Specificity (%)
MiR-21	0.811	0.738-0.884	0.037	5.80	97.30	59.34
MiR-93	0.810	0.726-0.894	0.043	4.71	59.46	91.21
MiR-21 + MiR-93	0.894	0.838-0.950	0.028	0.41	75.68	89.01

AUC: Area under the receiver operating characteristic curve; CI: Confidence interval.

Table 4 Correlation of clinical parameters and indexes of esophageal squamous cell carcinoma patients with radiotherapy and chemotherapy efficacy, n (%)

Category	n	Effective (n = 91)	Ineffective (n = 37)	χ2	P-value
Gender				0.058	0.810
Male	95	67 (73.63)	28 (75.68)
Female	33	24 (26.37)	9 (24.32)
Age (Yr)				0.404	0.525
≤ 65	54	40 (43.96)	14 (37.84)
> 65	74	51 (56.04)	23 (62.16)
Smoking history				5.733	0.017a
No	52	43 (47.25)	9 (24.32)
Yes	76	48 (52.75)	28 (75.68)
History of alcoholism				0.839	0.360
No	60	45 (49.45)	15 (40.54)
Yes	68	46 (50.55)	22 (59.46)
T stage				11.380	< 0.001b
T2/T3	98	77 (84.62)	21 (56.76)
T4	30	14 (15.38)	16 (43.24)
N stage				4.543	0.033a
N0	34	29 (31.87)	5 (13.51)
N1	94	62 (68.13)	32 (86.49)
M stage				13.900	< 0.001b
M0	100	79 (86.81)	21 (56.76)
M1	28	12 (13.19)	16 (43.24)
Tumor site				0.283	0.868
Upper 1/3 of thoracic part	44	30 (32.97)	14 (37.84)
Middle 1/3 of thoracic part	59	43 (47.25)	16 (43.24)
Lower 1/3 of thoracic part	25	18 (19.78)	7 (18.92)
Pathological differentiation				5.105	0.024a
Moderate/high differentiation	47	39 (42.86)	8 (21.62)
Low differentiation	81	52 (57.14)	29 (78.38)
Tumor length (cm)				0.592	0.442
≤ 5	30	23 (25.27)	7 (18.92)
> 5	98	68 (74.73)	30 (81.08)
MiR-21				14.870	< 0.001b
≤ 5.80	72	61 (67.03)	11 (29.73)
> 5.80	56	30 (32.97)	26 (70.27)
MiR-93				12.590	< 0.001b
≤ 4.71	99	78 (85.71)	21 (56.76)
> 4.71	29	13 (14.29)	16 (43.24)

^aP < 0.05 vs control group;

^bP < 0.01 vs control group.

Table 5 Assignment in logistic multivariate regression analysis

Factor	Variable	Assignment	Factor
Smoking history	X1	No = 1, Yes = 2	Smoking history
T stage	X2	T2/T3 = 1, T4 = 2	T stage
N stage	X3	N0 = 1, N1 = 2	N stage
M stage	X4	M0 = 1, M1 = 2	M stage
Pathological differentiation	X5	Moderate/high differentiation = 1, low differentiation = 2	Pathological differentiation
MiR-21	X6	≤ 5.80 = 1, > 5.80 = 2	MiR-21
MiR-93	X7	≤ 4.71 = 1, > 4.71 = 2	MiR-93

Table 6 Multivariate logistic regression analysis of factors affecting radiotherapy and chemotherapy efficacy in esophageal squamous cell carcinoma patients

Variable	B	SE	Wald	P-value	OR	95%CI
Smoking history	0.103	0.478	0.046	0.830	1.108	0.434-2.829
T stage	1.093	0.506	4.676	0.031a	2.984	1.108-8.037
N stage	0.954	0.713	1.792	0.181	2.597	0.642-10.502
M stage	1.047	0.454	5.312	0.021a	2.848	1.170-6.935
Pathological differentiation	0.644	0.600	1.155	0.283	1.905	0.588-6.168
MiR-21	1.901	0.602	9.961	0.002b	6.692	2.055-21.79
MiR-93	1.026	0.456	5.064	0.024a	2.791	1.142-6.823

^aP < 0.05,

^bP < 0.01 vs control group. OR: Odds ratio; CI: Confidence interval.

Table 7 Predictive value of plasma miR-21 and miR-93 for the 3-year overall survival in esophageal squamous cell carcinoma patients

Index	AUC	95%CI	SE	Cut-off	Sensitivity (%)	Specificity (%)
MiR-21	0.861	0.797-0.926	0.033	5.60	82.50	79.17
MiR-93	0.807	0.733-0.880	0.037	3.87	62.50	92.50

AUC: Area under the receiver operating characteristic curve; CI: Confidence interval.

Table 8 Univariate and multivariate Cox regression analyses of factors affecting 3-year overall survival of esophageal squamous cell carcinoma patients

Index	Univariate		Multivariate
	HR (95%CI)	P-value	HR (95%CI)	P-value
Gender (male vs female)	1.178 (0.508-2.686)	0.713
Age (≤ 65 yr vs > 65 yr)	1.167 (0.439-3.158)	0.770
Smoking history (no vs yes)	0.631 (0.259-1.483)	0.288
History of alcoholism (no vs yes)	0.802 (0.447-1.459)	0.468
T stage (T2/T3 vs T4)	3.183 (1.762-5.783)	< 0.001b	3.168 (1.537-6.537)	0.003b
N stage (N0 vs N1)	1.318 (1.067-1.638)	0.015a	1.307 (1.057-1.736)	0.017a
M stage (M0 vs M1)	2.438 (1.934-3.062)	< 0.001b	1.735 (1.402-2.281)	<0.001b
Tumor site (Upper 1/3 vs middle 1/3 vs lower 1/3 of thoracic part)	1.289 (0.557-2.825)	0.548
Pathological differentiation (moderate/high differentiation vs low differentiation)	0.753 (0.567-1.008)	0.048a	0.802 (0.557-1.159)	0.243
Tumor length (≤ 5 cm vs > 5 cm)	0.687 (0.283-1.675)	0.394
Radiotherapy and chemotherapy (effective vs ineffective)	1.695 (1.237-2.248)	0.001b	1.335 (0.975-1.846)	0.080
MiR-21 (≤ 5.60 vs > 5.60)	4.083 (2.158-7.763)	< 0.001b	2.438 (1.276-4.71)	0.007b
MiR-93 (≤ 3.87 vs > 3.87)	4.485 (1.993-10.067)	< 0.001b	2.198 (1.256-3.875)	0.009b

^aP < 0.05 vs control group;

^bP < 0.01 vs control group. HR: Hazard ratio; CI: Confidence interval.