NR2F6 Expression Correlates with Pelvic Lymph Node Metastasis and Poor Prognosis in Early-Stage Cervical Cancer

Abstract

Background: There is an abnormal expression of nuclear receptor subfamily 2 group F member 6 (NR2F6) in human cancers such as breast cancer, colon cancer, and acute myelogenous leukemia. However, its clinical significance in cervical cancer has not been established. We explored NR2F6 expression and its clinicopathological significance in early-stage cervical cancer. Methods: NR2F6 expression in cervical cancer cell lines and cervical cancer tissues was determined by Western blotting, real-time PCR, and immunochemistry (IHC). NR2F6 expression in 189 human early-stage cervical cancer tissue samples was evaluated using IHC. The relevance between NR2F6 expression and early-stage cervical cancer prognosis and clinicopathological features was determined. Results: There was marked NR2F6 mRNA and protein overexpression in the cervical cancer cells and clinical tissues compared with an immortalized squamous cell line and adjacent noncancerous cervical tissues, respectively. In the 189 cervical cancer samples, NR2F6 expression was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.006), squamous cell carcinoma antigen (p = 0.006), vital status (p < 0.001), tumor recurrence (p = 0.001), chemotherapy (p = 0.039), and lymph node metastasis (p < 0.001). Overall and disease-free survival was shorter in patients with early-stage cervical cancer and higher NR2F6 levels than in patients with lower levels of NR2F6. Univariate and multivariate analysis determined that NR2F6 was an independent prognostic factor of survival in early-stage cervical cancer. Conclusions: Taken together, our findings suggest that high NR2F6 expression predicts pelvic lymph node metastasis, tumor recurrence and poor prognosis in early-stage cervical cancer. NR2F6 might be a novel prognostic biomarker and potential therapeutic target of cervical cancer.

High expression of PTPRM predicts poor prognosis and promotes tumor growth and lymph node metastasis in cervical cancer

“…LNM is a key problem that significantly influence the clinical prognosis of patients with CCa [3][4][5] . Focusing on the crucial molecules which could exert pro-metastatic functions may help clinicians to understand the molecular mechanism of LNM and develop clinical therapeutic strategies.…”

“…Nearly 90% of cervical cancer occurred in developing countries in 2015 1,2 . Lymph node metastasis (LNM) is a key prognostic factor and the leading cause of death of CCa [3][4][5] . The 5-year overall survival rate of CCa patients decreases from 95% to 51% if with LNM, even when the CCa is treated with radical hysterectomy 6,7 .…”

<p>The Prognostic Significance Of Pretreatment Albumin/alkaline Phosphatase Ratio In Patients With Stage IB-IIA Cervical Cancer</p>

“…Although various guidelines recommend radiation therapy or concurrent chemoradiation therapy as the standard adjuvant therapy to reduce recurrence in patients with high or intermediate risk factors after radical hysterectomy, adjuvant therapies remain controversial. 42 Adjuvant chemotherapy alone may potentially reduce adverse events with the same efficacy as RT. 43 In our study, adjuvant chemotherapy was considered according to different pathological risk factors.…”

Cyr61 Expression Pattern and Association with Clinicopathological Factors in Patients with Cervical Cancer

“…For instance, in early-stage CC the protein TIMELESS could be associated with poor clinical outcome (17). Similarly, the nuclear receptor subfamily 2 group F member 6 (NR2F6) was identified as prognosticator for pelvic lymph node metastasis and poor outcome (18). The expression of Metadherin (MDTH) in CC tissues correlated with a higher risk of lymph node metastasis (19).…”