Down-regulated serum microRNA-101 is associated with aggressive progression and poor prognosis of cervical cancer

Wei Jiang; Jia-Jia Pan; Ying-Hui Deng; Mei-Rong Liang; Li-Hua Yao

doi:10.3802/jgo.2017.28.e75

Journal List > J Gynecol Oncol > v.28(6) > 1093862

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Jiang, Pan, Deng, Liang, and Yao: Down-regulated serum microRNA-101 is associated with aggressive progression and poor prognosis of cervical cancer

Original Article

J Gynecol Oncol 2017;28(6):e75.

Published online: 4 November 2017

DOI: https://doi.org/10.3802/jgo.2017.28.e75

Down-regulated serum microRNA-101 is associated with aggressive progression and poor prognosis of cervical cancer

Wei Jiang^1,, Jia-Jia Pan², Ying-Hui Deng³, Mei-Rong Liang¹, Li-Hua Yao^4,

¹Department of Gynecologic Oncology, Jiangxi Maternal and Child Health Hospital, Nanchang, China

²Department of Reproduction, Jiangxi Maternal and Child Health Hospital, Nanchang, China

³Department of Pathology, Jiangxi Maternal and Child Health Hospital, Nanchang, China

⁴School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, China

Correspondence to Wei Jiang Department of Gynecologic Oncology, Jiangxi Maternal and Child Health Hospital, No. 318 Bayi Avenue, Nanchang 330006, China. E-mail: jacky5824@163.com

Correspondence to Li-Hua Yao School of Life Science, Jiangxi Science & Technology Normal University, Fenglin Road 605, Economic Development District, Nanchang 330013, China. E-mail: yaolh79@yahoo.com

Received 14 May 2017 Revised 25 June 2017 Accepted 11 July 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

MicroRNAs (miRNAs) play a vital role in pathogenesis and progression of many cancers, including cervical cancer. However, importance of serum level of miR-101 in cervical cancer has rarely been studied. In the present study, clinical significance and prognostic value of serum miR-101 for cervical cancer was investigated.

Methods

Association between miR-101 level in cervical cancer tissues and prognosis of patients was analyzed by using data retrieved from The Cancer Genome Atlas (TCGA) database, which was followed with our clinical study in which miR-101 serum level comparison between cervical cancer patients and healthy controls was conducted by real-time quantitative polymerase chain reaction (PCR).

Results

TCGA database demonstrated that miR-101 was down-regulated in cervical cancer tissues compared with normal cervical tissues, and univariate Cox regression analysis indicated that decreased miR-101 expression was a highly significant negative risk factor. Similar trend was found in the serum miR-101. Serum level of miR-101 was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.003), lymph node metastasis (p=0.001), and serum squamous cell carcinoma antigen (SCC-Ag) level >4 (p=0.007). The overall survival time of cervical cancer patients with a higher level of serum miR-101 was significantly longer than that of patients with a lower level of serum miR-101. Moreover, multivariate Cox regression analysis indicated that the down-regulated serum level of miR-101 was an independent predictor for the unfavorable prognosis of cervical cancer.

Conclusion

Serum level of miR-101 is closely associated with metastasis and prognosis of cervical cancer; and, hence could be a potential biomarker and prognostic predictor for cervical cancer.

Keywords: miRNAs, Uterine Cervical Neoplasms, Serum, Prognosis, Gynecology, Disease Progression

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Fig. 1.

Expression level of miR-101 in cervical cancer was significantly decreased and positively associated with the prognosis of patients. (A) MiR-101 expression levels of cervical cancer patients (n=307) and healthy persons (n=3) from the TCGA database were analyzed. (B) The survival analysis for 2 groups of patients with low or high expression levels of miR-101. TCGA, The Cancer Genome Atlas.

Fig. 2.

The relative expression levels of miR-101 for 182 cervical cancer patients, before and after treatment, and 12 healthy women. The average value is indicated by the horizontal lines among the spots. The serum level of miR-101 was significantly higher in the healthy women compared with that from cervical cancer patients (p<0.001).

Fig. 3.

The association between serum miR-101 level and overall survival time was analyzed by Kaplan-Meier method. The survival period was shorter in the cervical cancer patients with a lower expression level of miR-101 (p=0.004).

Table 1.

Correlation of clinicopathological characteristics and serum miR-101 expression in the cervical cancer patients

Variables	No. of patients (n=182)	MiR-101 expression		p-value
Variables	No. of patients (n=182)	Low	High	p-value
Age (yr)				0.325
≤50	134	56 (41.8)	78 (58.2)
>50	48	24 (50.0)	24 (50.0)
FIGO stage				0.003
IB1–IIA1	153	60 (39.2)	93 (60.8)
IIA2–IIIB	29	20 (69.0)	9 (31.0)
Tumor size (cm)				0.123
≤4	150	62 (41.3)	88 (58.7)
>4	32	18 (56.3)	14 (43.7)
Histology				0.972
Squamous	139	61 (43.9)	78 (56.1)
Adenocarcinoma	43	19 (44.2)	24 (55.8)
Differentiation				0.078
Well-moderate	161	67 (41.6)	94 (58.4)
Poor	21	13 (61.9)	8 (38.1)
Lymph nodes metastasis				0.001
No	145	55 (37.9)	90 (62.1)
Yes	37	25 (67.6)	12 (32.4)
SCC-Ag (ng/L)				0.007
≤4	132	50 (37.9)	82 (62.1)
>4	50	30 (60.0)	20 (40.0)

Values are presented as number (%). FIGO, International Federation of Gynecology and Obstetrics; SCC-Ag, squamous cell carcinoma antigen.

Table 2.

Univariate and multivariate analyses of prognostic parameters in cervical cancer using the Cox regression model

Parameters	Univariable	Multivariable
Parameters	p-value	HR (95% CI)	p-value
MiR-101 expression			0.006
Low	0.004	2.820 (1.473–3.925)
High	–	–
Tumor size (cm)			–
≤4	0.192	–
>4	–	–
Differentiation			–
Well-moderate	0.260	–
Poor	–	–
SCC-Ag (μ g/L)			0.746
≤4	0.042	0.941 (0.452–2.103)
>4	–	–
FIGO stage			0.003
IB1–IIA1	0.031	2.378 (1.653–3.946)
IIA2–IIIB	–	–
Lymph nodes metastasis			0.015
No	0.042	2.023 (1.231–3.521)
Yes	–	–

CI, confidence interval; FIGO, International Federation of Gynecology and Obstetrics; HR, hazard ratio; SCC-Ag, squamous cell carcinoma antigen.

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