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

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

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.

References

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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.
jgo-28-e75f1.tif
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).
jgo-28-e75f2.tif
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).
jgo-28-e75f3.tif
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
Low High
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
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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