Affiliations: [a] Gynecology and Obstetrics Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China | [b] Gynecology and Obstetrics Department, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China | [c] Institute of Genetic Engineering, Southern Medical University, Guangzhou, Guangdong, China | [d] Biophysics Department, Oregon State University, Corvallis, OR, USA
Correspondence:
[*]
Corresponding author: Lin Lu, Gynecology and Obstetrics Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China. E-mail:[email protected]
Note: [1] The first two authors contributed equally to this work.
Abstract: BACKGROUND: Endometrial cancer (EC) is a common female
malignancy. Most patients were diagnosed at an early stage with a favorable
prognosis. But more than 30% patients were high risk at III/IV stage with
invading deep into the myometrium and progressively lead to local or extra
pelvic metastasis. Urothelial cancer-associated 1 (UCA1) had been reported
as the oncogenic long non-coding RNA in many tumors, but the role of UCA1 in
EC is still unclear. METHOD: QRT-PCR was used to analysis the level
of UCA1 in the proliferative endometrium, primary EC tissue and lymph
node metastasis tissue of EC. According to the QRT-PCR results of primary EC
tissue, survival curves were made using the Kaplan-Meier method, and the log
rank test was used to analyze the differences of clinicopathological
characteristics and survival between the low expression and high expression
group of UCA1 in EC patients. Moreover we knocked down the expression of
UCA1 in EC cell lines HTB-111 and Ishikawa, and detected the migration and
invasion ability of them with wound healing assay and transwell assay. RESULTS: The expression level of UCA1 using QRT-PCR method in lymph
node metastasis tissue was the highest than that in the proliferative
endometrium and primary EC tissues (1.15 ± 0.23, 3.23 ± 1.06 vs. 6.42 ± 1.46, P < 0.0001).
For the primary EC tissue, the median fold change of UCA1
was used as a cutoff value. High UCA1 expression was observed to be closely
correlated with lymph node metastasis (P = 0.008), distant metastasis (P = 0.003), grade (P = 0.009), advanced TNM stage (P = 0.031) and
vessel invasive (P = 0.032). The 5-year overall survival rate in the high
expression group was 41.7%, compared with 72.7% in the low expression
group (P = 0.023). After silencing the UCA1, the migration and invasion
ability of EC cell lines reduced significantly. CONCLUSION: Our
findings provide the convincing evidence that the UCA1 plays an important
role in the metastasis of EC and may serve as a novel molecular marker to
predict the aggressive tumor progression and unfavorable prognosis of EC
patients.
Keywords: Endometrial cancer, Long noncoding RNA, UCA1, metastasis
