Plasma miR-183 predicts recurrence and prognosis in patients with colorectal cancer

Figures & data

Figure 1. The expression levels of miR-183 in primary colorectal cancer (CRC) tissues and CRC cell lines. (A) The expression levels of miR-183 were significantly higher in CRC tissues than in paired normal colorectal tissues (P <0.001; Wilcoxon t-test). (B) The expression levels of miR-183 were significantly higher in CRC cell lines than in the normal colon cell line FHC and normal colorectal tissues (P <0.001; Mann-Whitney U-test). RNU6B (U6) was used as an internal control.

Figure 2. The miR-183 expression levels in plasma simples. (A) The miR-183 expression levels in plasma were significantly higher in colorectal cancer (CRC) patients (n = 118 ) than in healthy controls (n = 61 ) (P < 0.0001; Mann-Whitney U-test). (B) The miR-183 expression levels in the postoperative samples were significantly lower than those in the preoperative samples (p = 0 .001; Wilcoxon t-test). In three cases, the plasma miR-183 expression levels were re-elevated when patients developed postoperative recurrence. RNU6B (U6) was used as an internal control.

Figure 3. Comparison of the receiver operating characteristic (ROC) curves for miR-183 in the plasma and the conventional colorectal cancer biomarkers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19–9) in the serum.

Figure 4. Survival analysis of 118 colorectal cancer (CRC) patients grouped by their mean level of plasma miR-183. (A) The levels of plasma miR-183 in the high-expression and low-expression and controls groups. (B-C) Kaplan–Meier curves of 118 CRC patients showing the disease-free survival (DFS) and the overall survival (OS). The CRC patients with high miR-183 expression in the plasma displayed shorter DFS (P < 0.0001; log-rank test) and lower OS (p = 0 .0006; log-rank test).

Table 1. The relationship between plasma miR-183 expression and the clinicopathological characteristics

		miR-183 expression
	All	High	Low	p-value
Total	118 (100%)	50 (42.4%)	68 (57.6%)
Gender
Male	63 (53.4%)	27 (42.9%)	36 (57.1%)	0.909
Female	55 (46.6%)	23 (41.8%)	32 (58.2%)
Age
<60	59 (50.0%)	20 (33.9%)	39 (66.1%)	0.062
≥60	59 (50.0%)	30 (50.8%)	29 (49.2%)
Histology
Differentiated	66 (55.9%)	27 (40.9%)	39 (59.1%)	0.717
Undifferentiated	52 (44.1%)	23 (44.2%)	29 (55.8%)
Tumor depth
T1-T2	59 (50.0%)	22 (37.3%)	37 (62.7%)	0.264
T3-T4	59 (50.0%)	28 (47.5%)	31 (52.5%)
Lymph node metastasis
Negative	55 (46.6%)	18 (32.7%)	37 (67.3%)	0.048
Positive	63 (53.4%)	32 (50.8%)	31 (49.2%)
Distant metastasis
Negative	87 (73.7%)	30 (34.5%)	57 (65.5%)	0.004
Positive	31 (26.3%)	20 (64.5%)	11 (35.5%)
pTNM stage
I-II	43 (36.4%)	13 (30.2%)	30 (69.8%)	0.043
III-IV	75 (63.6%)	37 (49.3%)	38 (50.7%)
CEA
<3.5	59 (50.0%)	24 (40.7%)	35 (59.3%)	0.709
≥3 .5	59 (50.0%)	26 (44.1%)	33 (55.9%)
Tumor recurrence
Negative	81 (68.6%)	27 (33.3%)	54 (66.6%)	0.003
Positive	37 (31.4%)	23 (62.2%)	14 (37.8%)

pTNM, pathological tumor/node/metastasis.

Table 2. Univariate and multivariate analyses with regard to overall survival

	Univariate			Multivariate
	HR	95% CI	P-value	HR	95% CI	p-value
Gender
Male	1	Ref
Female	0.697	(0.426–1.139)	0.150
Age
<60	1	Ref
≥60	1.100	(0.674–1.797)	0.703
Histology
Differentiated	1	Ref
Undifferentiated	1.106	(0.673–1.817)	0.690
Tumor depth
T1-T2	1	Ref		1	Ref
T3-T4	1.939	(1.170–3.212)	0.010	1.076	(0.635–1.825)	0.784
Lymph node metastasis
Negative	1	Ref		1	Ref
Positive	7.937	(4.060–15.516)	<0.0001	1.986	(0.801–4.928)	0.139
Distant metastasis
Negative	1	Ref		1	Ref
Positive	5.098	(3.009–8.637)	<0.0001	2.055	(1.164–3.629)	0.013
pTNM stage
I-II	1	Ref		1	Ref
III-IV	12.116	(4.818–30.469)	<0.0001	5.218	(1.517–17.952)	0.009
CEA
<3.5	1	Ref
≥3 .5	1.375	(0.838–2.256)	0.207
miR-183
Low expression	1	Ref		1	Ref
High expression	2.302	(1.402–3.780)	0.001	1.831	(1.098–3.054)	0.021

HR, hazard ratio; CI, confidence interval; pTNM, pathological tumor/node/metastasis.

Table 3. Univariate and multivariate analyses with regard to tumor recurrence

	Univariate			Multivariate
	HR	95% CI	p-value	HR	95% CI	p-value
Gender
Male	1	Ref
Female	0.689	(0.363–1.327)	0.270
Age
<60	1	Ref
≥60	1.687	(0.872–3.261)	0.120
Histology
Differentiated	1	Ref
Undifferentiated	1.364	(0.716–2.600)	0.345
Tumor depth
T1-T2	1	Ref		1	Ref
T3-T4	4.088	(1.914–8.730)	<0.0001	2.213	(0.965–4.670)	0.061
Lymph node metastasis
Negative	1	Ref		1	Ref
Positive	5.168	(2.285–11.687)	<0.0001	0.933	(0.345–2.522)	0.891
Distant metastasis
Negative	1	Ref		1	Ref
Positive	3.568	(1.799–7.074)	<0.0001	1.529	(0.712–3.284)	0.276
pTNM stage
I-II	1	Ref		1	Ref
III-IV	18.733	(4.395–79.847)	<0.0001	11.782	(2.259–61.436)	0.003
CEA
<3.5	1	Ref		1	Ref
≥3 .5	2.084	(1.058–4.106)	0.034	1.447	(0.717–2.922)	0.303
miR-183
Low expression	1	Ref		1	Ref
High expression	3.370	(1.899–7.325)	<0.0001	3.448	(1.670–7.120)	0.001

HR, hazard ratio; CI, confidence interval; pTNM, pathological tumor/node/metastasis.

Figure 5. The miR-183 expression levels in hematocytes collected from 118 colorectal cancer (CRC) patients and 61 healthy controls. There was no significant difference in the miR-183 expression levels between CRC patients and healthy controls (p = 0 .1244; Mann-Whitney U-test). RNU6B (U6) was used as an internal control.