Circular RNAs (circRNAs) are novel type of noncoding RNAs that play important roles and serve as noninvasive biomarkers in various cancers. In the present study, we focused on circFoxO3a and aimed to investigate its prognostic value as a novel serum biomarker for squamous cervical cancer (SCC). Patients and Methods: Our study included 103 SCC patients from Obstetrics and Gynecology Hospital of Fudan University. Expression levels of circFoxO3a in the serum of patients with SCC were examined by reverse transcription-quantitative PCR (RT-qPCR). The correlation between serum circFoxO3a expression and clinicopathologic factors was analyzed. The Kaplan-Meier method and multivariate Cox regression analysis were applied to evaluate the independent prognostic factors for SCC. A prognostic predictive nomogram was constructed using R software. Results: Levels of serum circFoxO3a were decreased in SCC patients compared with controls. Low expression of circFoxO3a was correlated with deeper stromal invasion and positive lymph node metastasis. Moreover, SCC patients with lower expression of serum circFoxO3a showed poorer prognosis, including both overall survival (OS) and recurrencefree survival (RFS). Multivariate Cox analysis indicated low serum circFoxO3a levels to be an unfavorable prognostic factor for both OS and RFS, independent of positive lymph node metastasis. Notably, the predictive nomogram we established further confirmed that serum circFoxO3a is a useful tool for predicting survival in SCC. Conclusion: Altogether, our findings demonstrated that serum circFoxO3a could serve as a potential novel noninvasive predictive prognostic biomarker and therapeutic target for SCC.

Introduction Cervical cancer has high mortality, high recurrence and poor prognosis. Although prognostic biomarkers such as clinicopathological features have been proposed, their accuracy and precision are far from satisfactory. Therefore, novel biomarkers are urgently needed for disease surveillance, prognosis prediction and treatment selection. Materials Differentially expressed genes (DEGs) between cervical cancer and normal tissues from three microarray datasets extracted from the Gene Expression Omnibus platform were identified and screened. Based on these DEGs, a six‐gene prognostic signature was constructed using cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas. Next, the molecular functions and related pathways of the six genes were investigated through gene set enrichment analysis and co‐expression analysis. Additionally, immunophenoscore analysis and the QuartataWeb Server were employed to explore the therapeutic value of the six‐gene signature. Results We discovered 178 overlapping DEGs in three microarray datasets and established a six‐gene (APOC1, GLTP, ISG20, SPP1, SLC24A3 and UPP1) prognostic signature with stable and excellent performance in predicting overall survival in different subgroups. Intriguingly, the six‐gene signature was closely associated with the immune response and tumour immune microenvironment. The six‐gene signature might be used for predicting response to immune checkpoint inhibitors (ICIs) and the six genes may serve as new drug targets for cervical cancer. Conclusion Our study established a novel six‐gene (APOC1, GLTP, ISG20, SPP1, SLC24A3 and UPP1) signature that was closely associated with the immune response and tumour immune microenvironment. The six‐gene signature was indicative of aggressive features of cervical cancer and therefore might serve as a promising biomarker for predicting not only overall survival but also ICI treatment effectiveness. Moreover, three genes (UPP1, ISG20 and GLTP) within the six‐gene signature have the potential to become novel drug targets.

Objective To evaluate the prognostic performance of the revised 2018 FIGO staging system for cervical cancer. Methods This retrospective multicenter study enrolled cervical cancer patients with 2009 FIGO Stage IA1–IIA2 who underwent surgeries between January 2006 and December 2017 in four tertiary hospitals. Patients were restaged according to the 2018 FIGO staging system by reviewing their medical data. Results Of 3238 cervical cancer patients included, 1841 (56.9%) patients were restaged: 641 (34.9%) due to tumor size, 544 (29.5%) due to lymph node metastasis, 614 (33.4%) due to the inconsistency between pre‐ and postoperative assessments, and 42 due to the cancellation of invasion width in Stage IA. After restaging, a clear tendency of decreased recurrence‐free survival (RFS) and overall survival (OS) with increasing stage was observed. Multivariate Cox analysis showed that 2018 FIGO stage, parametrial involvement, and histology were independent prognostic factors for both OS and RFS (P < 0.05). Based on these factors, we established predictive nomograms with c‐indexes of 0.735 and 0.721, showing good predictive ability for cervical cancer. Conclusion The revised 2018 FIGO staging system can better reflect the survival of cervical cancer patients. Based on it, we established a nomogram that can predict the prognosis of cervical cancer patients more precisely.