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Recently, there has been growing interest among researchers in exploring the effects of epithelial-mesenchymal transformation (EMT) or N6-Methyladenosine (m6A) modification regulators on tumor development. However, the synergistic efficiency of these regulators in relation to ovarian cancer development remains unclear. This study aims to explore the transcription patterns of main regulators, including 19 EMT and 22 m6A, in ovarian cancer samples from TCGA datasets and normal samples from GTEx datasets. After conducting a LASSO regression analysis, ten prognostic signatures were identified, namely KIAA1429, WTAP, SNAI1, AXL, IGF2BP1, ELAVL1, CBLL1, CDH2, NANOG and ALKBH5. These signatures were found to have a comprehensive effect on immune infiltrating signatures and the final prognostic outcome. Next, utilizing the ssGSEA algorithm and conducting overall survival analyses, we have identified the key prognosis-related immunological signatures in ovarian cancer to be ALKBH5, WTAP, ELAVL1, and CDH2 as the regulators. The characteristic immune response and related genetic expression have revealed a significant correlation between the alteration of m6A regulators and EMT regulators, indicating a synergistic effect between these two factors in the development of ovarian cancer. In summary, our research offers a novel perspective and strategy to enhance the occurrence, progression, and prognosis of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Although the effect of pseudogene ANXA2P2 on some tumors has been reported in a few literatures, the therapeutic potential and prognostic value of ANXA2P2 in ovarian serous cystadenocarcinoma (OV) have not been elucidated. Methods: The correlation for ANXA2P2 expression patterns to prognostic characteristics, tumor immune microenvironment, immune cell infiltration level, tumor mutation burden (TMB), tumor microsatellite instability (MSI), drug sensitivity, and pathway function enrichment were investigated in pan-carcinoma via TCGA and GTEx databases. Subsequently, the role of ANXA2P2 expression levels in the pathway enrichments and prognosis prediction in OV were further explored using weighted correlation network analysis (WGCNA) analysis, gene mutation analysis, and risk-independent prognostic analysis. Results: ANXA2P2 was frequently overexpressed in a variety of tumors compared with normal tissues. The correlation analysis for prognostic characteristics, tumor immune microenvironment, immune cell infiltration level, TMB, MSI, drug sensitivity, and pathway function enrichment revealed that ANXA2P2 expression patterns might deal a significant impact on the pathogenesis, development, and prognosis of various tumors. Then, GSVA, GSEA, WGCNA, gene mutation, and independent prognostic analysis for OV have indicated that high expression in ANXA2P2 could be mostly enriched in TNF-α signaling- via -NF-κB, epithelial-mesenchymal transition, apical junction, IL-6-JAK STAT3 signaling, etc., which were also proved to act as crucial factors on tumorigenesis, development, invasion, and metastasis. The mutation of TP53 (94%), TTN (24%), and CSMD3 (9%) in the biological process of tumor had been confirmed by relevant studies. Finally, the independent prognostic analysis demonstrated that ANXA2P2 expression in OV contributes greatly to the dependability of 3- and 5-year survival prediction. Conclusion: In summary, our findings might provide a helpful foundation for prospective explorative researches, afford new strategies for the clinical treatment, deal prognosis prediction, and give new hope for OV patients. [ABSTRACT FROM AUTHOR]

Background: KIF20A plays an indispensable role in cytokinesis regulation, which is important for tumor proliferation and growth. Recently, the oncogenic role of KIF20A has been well documented in several cancers. However, its clinical role in epithelial ovarian cancer (EOC) remains not reported yet. We investigated its expression and its role in promoting invasion and chemoresistance in EOC cells.Patients and methods: KIF20A transcription and translation levels were investigated in normal ovarian epithelial cell, ovarian cancer cells, and 10 pairs of fresh EOC tissues and adjacent normal ovarian tissues by real-time quantitative polymerase chain reaction and Western blots. Moreover, KIF20A protein level was also examined by immunohistochemistry in 150 EOC tissues. The correlation between KIF20A expression and clinical variables was analyzed by statistical methods. We also used wound healing assay, transwell assay MTT, and Annexin V/PI to explore KIF20A functions.Results: KIF20A expression was obviously elevated at both mRNA and protein levels in EOC cell lines and clinical cancer tissues compared with normal ovarian epithelial cell and adjacent normal ovarian tissues. KIF20A protein expression was highly correlated with International Federation of Gynecology and Obstetrics stage (P=0.008), lymph node metastasis (P=0.002), intraperitoneal metastasis (P<0.001), vital status at last follow-up (P<0.001), intraperitoneal recurrence (P=0.030), tumor recurrence (P=0.005), drug resistance (P=0.013), and ascites with tumor cells (P<0.001). KIF20A overexpression was closely related to poorer overall survival and disease progression-free survival. Furthermore, Cox regression analysis revealed that KIF20A can act as an independent hazard indicator for predicting clinical outcomes in EOC patients. Interestingly, KIF20A overexpression promoted invasion and metastasis of EOC cells and also confers resistance to cisplatin.Conclusion: Our findings indicated that KIF20A overexpression predicts unfavorable clinical outcome, revealing that KIF20A holds a promising potential to serve as a useful prognostic biomarker for EOC patients. [ABSTRACT FROM AUTHOR]

Centrosomal protein 55 (CEP55) is a cell cycle regulator implicated in development of certain cancers. However, characteristics of CEP55 expression and its clinical/prognostic significance are unclear in human epithelial ovarian carcinoma (EOC). Therefore, we investigated the expression and clinicopathological significance of CEP55 in patients with EOC and its role in regulating invasion and metastasis of ovarian cell lines. CEP55 mRNA and protein expression levels were detected by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Potential associations of CEP55 expression scores with clinical parameters and patient survival were evaluated. CEP55 function was investigated further using RNA interference, wound healing assay, transwell assay, immunofluorescence analysis, qRT-PCR, and Western blotting. CEP55 was significantly upregulated in ovarian cancer cell lines and lesions compared with normal cells and adjacent noncancerous ovarian tissues. In the 213 EOC samples, CEP55 protein levels were positively correlated with clinical stage ( P < 0.001), lymph node metastasis ( P < 0.001), intraperitoneal metastasis ( P < 0.001), tumor recurrence ( P < 0.001), differentiation grade ( P < 0.001), residual tumor size ( P < 0.001), ascites see tumor cells ( P = 0.020), and serum CA153 level ( P < 0.001). Moreover, patients with aberrant CEP55 protein expression showed tendencies to receive neoadjuvant chemotherapy ( P < 0.001) and cytoreductive surgery ( P = 0.020). By contrast, no significant correlation was detected between the protein levels and patient age, histological type, or serum CA125, CA199, CA724, NSE, CEA, and β-HCG levels. Patients with high CEP55 protein expression had shorter overall survival and disease-free survival compared with those with low CEP55 expression. Multivariate analysis implicated CEP55 as an independent prognostic indicator for EOC patients. Additionally, downregulation of CEP55 in ovarian cancer cells remarkably inhibited cellular motility and invasion. Aberrant CEP55 expression may predict unfavorable clinical outcomes in EOC patients and play an important role in regulating invasion in ovarian cancer cells. Thus, CEP55 may serve as a prognostic marker and therapeutic target for EOC. [ABSTRACT FROM AUTHOR]

Anlotinib is a novel multi-target tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A previous retrospective study achieved the overall response rate (ORR) of 14.3% and the disease control rate (DCR) of 85.7% in platinum-resistant ovarian cancer (PROC) patients (pts) treated with anlotinib monotherapy, and the ORR of 33.3% and the DCR of 100% with anlotinib plus chemotherapy. The current prospective clinical trial (ChiCTR1800018192) aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed and continued as maintenance therapy for PROC. Pts who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-refractory or platinum-resistant epithelial ovarian cancer (including fallopian tube carcinoma and primary peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14) orally plus pemetrexed intravenously (0.5 g/m2 on day 1). Anlotinib monotherapy was subsequently performed up to 1 year in patients without disease progression or intolerable toxicity. The primary endpoint was ORR, and the secondary endpoints included DCR, progression-free survival (PFS) and safety. As of October 2020, 22 pts were enrolled. The median prior lines of chemotherapy was 4 (range, 2-10) and 55% of pts had ever received antiangiogenic therapy. A total of 17 pts had the confirmed best overall response assessments which inferred the ORR of 41.2% (PR in 7 pts; 95% CI, 18.4-67.1) and the DCR of 100% (PR in 7 pts and SD in 10 pts; 95% CI, 80.5-100). The median PFS was 9.3 months (95% CI, 6.0-12.6). Any grades of adverse events (AEs) were observed in 91% (20/22) of pts, containing frequent hand-foot syndrome (36%), hypertension (32%), allergic eruption (27%), fatigue (23%) and oral ulcer (14%). High grade AEs occurred in 3 pts, including 1 with grade III proteinuria, 1 with grade III ascites increase, and 1 with grade IV hemoglobin reduction. The treatment of anlotinib plus pemetrexed showed encouraging efficacy and satisfactory safety for platinum-resistant and -refractory, recurrent ovarian cancer pts who were previously treated with chemotherapy. [ABSTRACT FROM AUTHOR]