Many studies have intensely focused on the function of altered miRNA expression in human cancer in recent years [
16]. Some miRNAs in cancer cells could play a role as oncogenes to inhibit the expression of tumor suppressors [
17]. Moreover, the physiological and pathological roles of miRNAs have also been demonstrated in most tumor types and miRNAs may play an important role in the diagnosis, prognosis, and treatment of cancer [
7],[
18]. Therefore, the correlations between miRNAs and cancers have become a focus of cancer studies. Previously, researchers have found that disregulation of several miRNAs are associated with the prognosis in patients with cancer, suggesting that miRNA expression level detection might become a potential biomarker of prognosis in cancer [
19]-[
23].
miR-22 is located at a fragile cancer-relevant genomic region in chromosome 17 (17p13.3), and is mapped to an exon of the C17orf91 gene [
24]. This miRNA plays unique roles in specific cell types. For example, it regulates PPARalpha and BMP7 signaling pathways in human chondrocytes [
25], and the differentiation of a monocyte cell line [
26]. Recent studies have demonstrated that miR-22 is deregulated in many types of cancers and is involved in various cellular processes related to carcinogenesis, including cell growth, apoptosis, motility, and cell cycle. Zhang et al. indicated that miR-22 was downregulated in HCC and had considerable potential in identification of the prognosis [
10]; Xiong et al. found that miR-22 was also downregulated in breast cancer, and it suppressed breast cancer development through directly targeting oestrogen receptor ? (ER?) and downstream signaling [
11]; Wang et al. offered the convincing evidence that the reduced expression of miR-22 was significantly associated with malignant development of gastric cancer and may be a novel prognostic marker [
8]; Yamakuchi et al. found that miR-22 expression in human colon cancer was lower than in normal colon tissues, and it might have an anti-angiogenic effect in this cancer [
27]; Ling et al. observed the downregulation of miR-22 in lung cancer tissues and lung cancer cell lines, and also suggested that miR-22 might exhibit excellent anti-lung cancer activity in vitro and in vivo [
28]. However, miR-22 expression was suggested to be upregulated in prostate cancer, and its upregulation potentiated phosphatidylinositol 3-kinase-Akt pathway activation [
29]. These controversial results of miR-22 in cancer development may reflect the diverse roles of miR-22 in different types of cancers.
Previously, Li et al. found that there was a negative correlation between miR-22 expression and the metastatic potential in ovarian cancer cells. Furthermore, both gain-of-function and loss-of-function studies displayed an inhibitory effect of miR-22 on cell migration and invasion in vitro without significantly affecting cell viability and apoptosis. Subsequent bioinformatics analysis revealed that miR-22 might regulate multiple pro-metastatic genes, which could provide an explanation to the inhibitory effects of miR-22 on cell migration and invasion. Taken together, their findings suggested that miR-22 might be involved in inhibiting ovarian cancer metastasis [
30]. However, the clinical significance and prognostic value of miR-22 in EOC haven't been investigated. Hence, in the present study, we focused on the expression and clinical significance of miR-22 in EOC. We found that miR-22 expression in EOC tissues was significantly lower than that in matched normal adjacent tissues. Then the relationships of the miR-22 with various clinical features of EOC were analyzed. We found that low miR-22 expression level was correlated with FIGO stage, tumor grade, and lymph node metastases, suggesting that miR-22 might be involved in the carcinogenesis and metastasis of EOC. Furthermore, Kaplan-Meier analysis with the log-rank test indicated that low miR-22 expression had a significant impact on overall survival and progression-free survival. Univariate and multivariate analyses were utilized to evaluate whether the miR-22 expression level and various clinicopathological features were independent prognostic parameters of EOC patient outcomes. Multivariate analysis revealed that miR-22 expression level was independent prognostic factors for overall survival, as well as progression-free survival of EOC patients, indicating that low miR-22 level was a promising non-invasive biomarker for prognosis of patients with EOC.