Ovarian cancer is one of the most common gynecologic cancers that has the highest mortality rate. Endometrioid ovarian cancer, a distinct subtype of epithelial ovarian cancer, is associated with endometriosis and Lynch syndrome, and is often accompanied by synchronous endometrial carcinoma. In recent years, dysbiosis of the microbiota within the female reproductive tract has been suggested to be involved in the pathogenesis of endometrial cancer and ovarian cancer, with some specific pathogens exhibiting oncogenic having been found to contribute to cancer development. It has been shown that dysregulation of the microenvironment and accumulation of mutations are stimulatory factors in the progression of endometrioid ovarian carcinoma. This would be a potential therapeutic target in the future. Simultaneously, multiple studies have demonstrated the role of four molecular subtypes of endometrioid ovarian cancer, which are of particular importance in the prediction of prognosis. This literature review aims to compile the potential mechanisms of endometrioid ovarian cancer, molecular characteristics, and molecular pathological types that could potentially play a role in the prediction of prognosis, and the novel therapeutic strategies, providing some guidance for the stratified management of ovarian cancer.
Alternative splicing (AS) is a universal post-transcriptional regulation process in cells, and increasing evidences have validated its crucial role in tumors. We collected AS event, gene expression, and clinical data of 178 AML patients from The Cancer Genome Atlas (TCGA) project. More than 1,000 AS events were found associated with overall survival (OS), and alternate promoter (AP) events were the most significant. The expression of the KIAA0930 transcript was the most significantly different AS event selected from AP events and significantly correlated with the expression of the splicing factor (SF) polypyrimidine tract-binding protein 1 (PTBP1). Then, the roles of PTBP1 on AS of the KIAA0930 and the proliferation of AML cells were confirmed. KIAA0930 variant 1 (KIAA0930-1) was upregulated and variant 2 (KIAA0930-2) downregulated with knockdown PTBP1 expression of AML cells by specific shRNA. A low level of PTBP1 can decrease the proliferation ability of AML cells. In conclusion, the results showed that PTBP1 might be a potential target for AML therapy.
Reticulocalbin-1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) from AML patients but does not affect the viability of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from healthy donors in vitro. Downregulation of RCN1 also reduces the viability of AML cell lines. Further studies showed that the RCN1 knockdown upregulates type I interferon (IFN-1) expression and promotes AML cell pyroptosis through caspase-1 and gasdermin D (GSDMD) signaling. Deletion of the mouse Rcn1 gene inhibits the viability of mouse AML cell lines but not the hematopoiesis of mouse bone marrow. In addition, RCN1 downregulation in human AML cells significantly inhibited tumor growth in the NSG mouse xenograft model. Taken together, our results suggest that RCN1 may be a potential target for AML therapy.
Cervical squamous cell carcinoma (CSCC) is one of the leading causes of cancer death in women worldwide. Patients with advanced cervical carcinoma always have a poor prognosis once resistant to cisplatin due to the lack of effective treatment. It is urgent to investigate the molecular mechanisms of cisplatin resistance. Circular RNAs (circRNAs) are known to exert their regulatory functions in a series of malignancies. However, their effects on CSCC remain to be elucidated. Here, we found that cytoplasmic circARHGAP5, derived from second and third exons of the ARHGAP5 gene, was downregulated in cisplatin-resistant tissues compared with normal cervix tissues and untreated cervical cancer tissues. In addition, experiments from overexpression/knockdown cell lines revealed that circARHGAP5 could inhibit cisplatin-mediated cell apoptosis in CSCC cells both in vitro and in vivo. Mechanistically, circARHGAP5 interacted with AU-rich element RNA-binding protein (AUF1) directly. Overexpression of AUF1 could also inhibit cell apoptosis mediated by cisplatin. Furthermore, we detected the potential targets of AUF1 related to the apoptotic pathway and found that bcl-2-like protein 11 (BIM) was not only negatively regulated by AUF1 but positively regulated by circARHGAP5, which indicated that BIM mRNA might be degraded by AUF1 and thereby inhibited tumor cell apoptosis. Collectively, our data indicated that circARHGAP5 directly bound to AUF1 and prevented AUF1 from interacting with BIM mRNA, thereby playing a pivotal role in cisplatin resistance in CSCC. Our study provides insights into overcoming cancer resistance to cisplatin treatment.
Ovarian clear cell carcinoma (OCCC) is a special subtype of epithelial ovarian carcinoma with unique characteristics and no specific tumour markers. Due to the inherent chemoresistance, there are no effective chemotherapy regimen for OCCC, resulting in the extremely poor prognosis of patients, especially at advanced stage. Therefore, the purpose of our research is to investigate the clinical characteristics and outcomes of ovarian clear cell carcinoma (OCCC) and to provide additional supporting evidence to aid in the clinical diagnosis and management.
Methodology
This was a retrospective study investigating the clinical characteristics and survival outcomes of 87 patients with OCCC treated at The First Affiliated Hospital of University of Science and Technology of China (USTC), between January 2010 and March 2020. Survival analysis was also performed on 179 patients with OCCC diagnosed between 1975 and 2017, obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry database.
Results
The median age of study participants was 49.28 ± 9.8 years old, with 74.71% diagnosed at an early stage. Median CA125 level was 607.26 IU/mL, with 23.94% having a normal CA125 level. 16 patients (18.39%) had co-existing endometriosis and 8 patients (9.2%) had a preoperative history or developed postoperative complications of venous thromboembolism (VTE). Surgical staging procedures were performed on 65 patients and cytoreduction was performed on 22 patients, among whom 17 patients received optimal cytoreduction. 67 patients (77.01%) underwent lymphadenectomy, and only 3 (4.48%) were found to have positive lymph nodes. Positive HNF1β, and negative WT-1, ER, and PR are reliable immunohistochemical indicators of OCCC. Patients diagnosed at an early stage had higher 3-year overall survival (OS) (89.47% vs. 44.44%) and progression-free survival (PFS) rates (78.95% vs. 22.22%) than those with advanced stage OCCC at diagnosis. CA199 (P = 0.025) and ascites (P = 0.001) were significantly associated with OS, while HE4 (P = 0.027) and ascites (P = 0.001) were significantly associated with PFS. Analysis of data from the SEER database showed that the presence of positive lymph nodes is also an independent prognostic factor for OS (P = 0.001).
Conclusion
OCCC often presents at an early stage and young age with a mild elevation in CA125 level. CA199, HE4, massive ascites and positive lymph node are independent prognostic factors for overall survival in OCCC.
Disclosures
This work was supported by the National Natural Science Foundation of China (81872110, 81902632), National Key Research and Development Program (2018YFC1003900), Anhui Provincial Key Research and Development Program (1704a0802151). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. No conflicts of interest to disclose.
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