High expression of miR-221 indicates poor prognosis in patients with intrahepatic cholangiocarcinoma

doi:10.3877/cma.j.issn.2095-3232.2019.06.015

Abstract

Abstract:

Objective

To observe the expression profile of miRNAs in intrahepatic cholangiocarcinoma (ICC), and to explore its value in predicting the survival and prognosis of ICC patients.

Methods

The tissue specimens were obtained from 134 patients with ICC or with combined hepatocellular and cholangiocarcinoma (cHCC-CC) receiving surgical resection in Sun Yat-sen University Cancer Center from April 2000 to September 2014. Normal bile duct tissues were collected from 5 patients as controls. The expression levels of miR-221, miR-675, miR-1248 and miR-1292 in tumor tissues were quantitatively detected by qRT-PCR and the clinicopathological characteristics were analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Correlation analysis was performed by Chi-square test. Survival analysis was performed by using Kaplan-Meier method and Log-rank test. Factors that may affect the prognosis were subject to univariate and multivariate analyses using Cox's proportional hazard model.

Results

Among 134 patients, ICC patients accounted for 63.4% (85/134) and cHCC-CC patients 36.6% (49/134). The proportion of patients with high expression of miR-221, miR-675, miR-1248 and miR-1292 in tumor tissues were 43.3%, 44.0%, 77.6% and 59.7%, respectively. The expression level of miR-221 was significantly correlated with the metastasis of tumor lymph node, and patients with high expression presented with a high incidence of lymph node metastasis (χ²=7.65, P<0.05). Multivariate analysis demonstrated that high expression of miR-221 was an independent risk factor for the overall survival of patients (HR=1.878, 95%CI: 1.135-3.106; P<0.05). The median overall survival time of patients with high expression of miR-221 was 14.5 months and 34.0 months for those with low expression of miR-221. The prognosis was worse for patients with high expression (χ²=8.87, P<0.05).

Conclusions

High expression of miR-221 is an independent risk factor for clinical prognosis of ICC patients, indicating a poor prognosis in ICC patients.

Key words: Bile duct neoplasms, Intrahepatic cholangiocarcinoma, MicroRNAs, Prognosis

Yuhao Tang, Juncheng Wang, Meiyin Zhang, Yingqin Zhu, Jinbin Chen, Yaojun Zhang, Zhongguo Zhou, Minshan Chen, Li Xu. High expression of miR-221 indicates poor prognosis in patients with intrahepatic cholangiocarcinoma[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2019, 08(06): 533-537.

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References 30

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miRNAs	相对表达量	例（%）
miRNA-221	0.8（0.3, 2.2）	?
?	≤1	76（56.7%）
?	>1	58（43.3%）
miRNA-675	0.8（0.2, 3.4）	?
?	≤1	75（56.0%）
?	>1	59（44.0%）
miRNA-1248	2.8（1.1, 6.6）	?
?	≤1	30（22.4%）
?	>1	104（77.6%）
miRNA-1292	1.3（0.5, 3.7）	?
?	≤1	54（40.3%）
?	>1	80（59.7%）

miRNAs	相对表达量	例（%）
miRNA-221	0.8（0.3, 2.2）	?
?	≤1	76（56.7%）
?	>1	58（43.3%）
miRNA-675	0.8（0.2, 3.4）	?
?	≤1	75（56.0%）
?	>1	59（44.0%）
miRNA-1248	2.8（1.1, 6.6）	?
?	≤1	30（22.4%）
?	>1	104（77.6%）
miRNA-1292	1.3（0.5, 3.7）	?
?	≤1	54（40.3%）
?	>1	80（59.7%）

?	DFS			OS
	单因素	多因素		单因素	多因素
	P值	HR（95%CI）	P值	P值	HR（95%CI）	P值
GGT>50 U/L	0.010	?	?	<0.001	1.990(1.109～3.569)	0.021
CEA>5 μg/L	0.002	?	?	<0.001	1.675(1.026～2.735)	0.039
肿瘤直径>5 cm	<0.001	1.941(1.224～3.027)	0.003	<0.001	2.367(1.407～3.981)	0.001
淋巴结转移	<0.001	2.802(1.536～5.110)	0.001	<0.001	2.547(1.407～4.608)	0.002
miRNA-221>1	0.009	?	?	0.003	1.878(1.135～3.106)	0.014

?	DFS			OS
	单因素	多因素		单因素	多因素
	P值	HR（95%CI）	P值	P值	HR（95%CI）	P值
GGT>50 U/L	0.010	?	?	<0.001	1.990(1.109～3.569)	0.021
CEA>5 μg/L	0.002	?	?	<0.001	1.675(1.026～2.735)	0.039
肿瘤直径>5 cm	<0.001	1.941(1.224～3.027)	0.003	<0.001	2.367(1.407～3.981)	0.001
淋巴结转移	<0.001	2.802(1.536～5.110)	0.001	<0.001	2.547(1.407～4.608)	0.002
miRNA-221>1	0.009	?	?	0.003	1.878(1.135～3.106)	0.014

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