Down-regulated expression of is associated with lymph node metastasis and predicts poor outcome in stage IB cervical squamous cell carcinoma: a case-control study.

Background: Lymph node metastasis (LNM) accounts for the most important route of metastasis for cervical cancer. Yet, the status of LNM is different in patients with similar clinico-pathological variables. It has been revealed that microRNAs are widely involved in the occurrence and development of various malignancies, and the tumor-suppressive or promoting effects of () family have been previously reported. This study sought to investigate the predictive value of for lymphogenous spread and its effect on the survival of patients with early-stage cervical squamous cell cancer (CSCC).

Methods: Patients with stage IB squamous cervical cancer who were treated surgically between October 2015 and November 2018 were enrolled. A total of 21 formalin-fixed paraffin-embedded tissues of pathologically confirmed positive lymph nodes were retrieved, and an additional 21 tissues of negative lymph nodes from patients well-matched on baseline characteristics were collected as the control group. TaqMan real-time quantitative polymerase chain reaction was used to examine the expression levels of in the samples. Differential expression levels of were compared between the 2 groups using independent sample t-test. Furthermore, the associations between expression level and clinico-pathological parameters of these 42 patients was evaluated by Chi-square test or Fisher's exact-probability method, and their effects on survival were assessed using Kaplan-Meier product-limit method.

Results: There were no significant differences in baseline clinico-pathological parameters between the 2 groups (P>0.05). The expression levels of in the node-positive group and control group were 1.61±3.09 and 16.77±30.40, respectively (P=0.029). Downregulated expression of was closely related to depth of invasion (DOI) and lymph-vascular space invasion (P<0.05). Univariate analysis revealed that downregulated and deeper DOI were associated with worse 5-year disease-free survival, while multivariate analysis showed that only the expression level of was an independent factor for disease-free survival (HR =0.120; 95% CI: 0.015-0.979; P=0.048). Patients with downregulated tended to have more unfavorable overall survival, but the difference did not reach statistical significance.

Conclusions: plays an inhibitory role in the pathogenesis of lymph node metastasis and may serve as a novel prognostic biomarker for patients with CSCC.