Meigs syndrome with pleural effusion as initial manifestation: A case report.

BACKGROUND: Meigs syndrome is a rare neoplastic disease characterized by the triad of benign solid ovarian tumor, ascites, and pleural effusion. In postmenopausal women with pleural effusions, ascites, elevated CA-125 level, and pelvic masses, the probability of disseminated disease is high. Nevertheless, the final diagnosis is based on its histopathologic features following surgical removal of a mass lesion. Here we describe a case of Meigs syndrome with pleural effusion as the initial manifestation. CASE SUMMARY: A 52-year-old woman presented with a 2-mo history of dry cough and oppression in the chest and was admitted to our hospital due to recurrent pleural effusion and gradual worsening of dyspnea that had occurred over the previous month. Two months before admission, the patient underwent repeated chest drainage and empirical anti-tuberculosis treatment. However, the pleural fluid accumulation persisted, and the patient began to experience dyspnea on exertion leading to admission. A computed tomography scan of the chest, abdominal ultrasound, and magnetic resonance imaging confirmed the presence of right-sided pleural effusion and ascites with a right ovarian mass. Serum tumor markers showed raised CA-125. With a suspicion of a malignant tumor, the patient underwent laparoscopic excision of the ovarian mass and the final pathology was consistent with an ovarian fibrothecoma. On the seventh day postoperation, the patient had resolution of the right-sided pleural effusion. CONCLUSION: Despite the relatively high risk of malignancy when an ovarian mass associated with hydrothorax is found in a patient with elevated serum levels of CA-125, clinicians should be aware about rare benign syndromes, like Meigs, for which surgery remains the preferred treatment.

EZH2 activates CHK1 signaling to promote ovarian cancer chemoresistance by maintaining the properties of cancer stem cells.

Background: Ovarian cancer is a fatal malignant gynecological tumor. Ovarian cancer stem cells (OCSCs) contribute to resistance to chemotherapy. The polycomb group protein enhancer of zeste homolog 2 (EZH2) plays a key role in maintaining CSCs. Here, we aimed to investigate the specific mechanism by which EZH2 regulates CSCs to result in chemoresistance and poor prognosis of ovarian cancer. Methods: We used a nude mouse model to obtain a cell line enriched for OCSCs, named SK-3rd cells. The CRISPR and Cas9 endonuclease system was used to establish an EZH2-knockout SK-3rd ovarian cancer cell line. High-throughput PCR array and bioinformatics methods were used to screen the EZH2 target involved in CSC stemness. A luciferase reporter assay and chromatin immunoprecipitation assay were performed to identify activation of CHK1 by EZH2. We evaluated associations between EZH2/CHK1 expression and the chemoresistance and prognosis of ovarian cancer patients. Results: EZH2 plays a critical role in maintaining ovarian CSC stemness and chemo-resistance. CHK1 is an EZH2 target involved in CSC stemness. Knockdown of EZH2 in ovarian CSCs decreased CHK1 expression, while CHK1 overexpression was sufficient to reverse the inhibitory effect on spheroid formation and chemoresistance caused by repression of EZH2. In addition, EZH2 was also shown to play a unique role in activating rather than repressing CHK1 signaling through binding to the CHK1 promoter in epithelial ovarian cancer cells. Finally, in clinical samples, ovarian cancer patients with high levels of EZH2 and CHK1 not only were more resistant to platinum but also had a poorer prognosis. Conclusions: Our data revealed a previously unidentified functional and mechanistic link between EZH2 levels, CHK1 signaling activation, and ovarian CSCs and provided strong evidence that EZH2 promotes ovarian cancer chemoresistance and recurrence.

Role of EZH2 in cancer stem cells: from biological insight to a therapeutic target.

Epigenetic modifications in cancer stem cells largely result in phenotypic and functional heterogeneity in many solid tumors. Increasing evidence indicates that enhancer of zeste homolog 2 (EZH2), the catalytic subunit of Polycomb repressor complex 2, is highly expressed in cancer stem cells of numerous malignant tumors and has a critical function in cancer stem cell expansion and maintenance. Here, we review up-to-date information regarding EZH2 expression patterns, functions, and molecular mechanisms in cancer stem cells in various malignant tumors and discuss the therapeutic potential of targeting EZH2 in tumors.

SOX2 is required to maintain cancer stem cells in ovarian cancer.

Ovarian cancer cells can form spheroids under serum-free suspension culture conditions. The spheroids, which are enriched in cancer stem cells, can result in tumor dissemination and relapse. To identify new targetable molecules in ovarian cancer spheroids, we investigated the differential expression of genes in spheroids compared with that under monolayer culture conditions by qPCR microarray. We identified that SOX2 is overexpressed in spheroids. We then proved that SOX2 expression was increased in successive spheroid generations. Besides, knockdown of SOX2 expression in SKOV3 or HO8910 ovarian cancer spheroid cells decreased spheroid formation, cell proliferation, cell migration, resistance to Cisplatin treatment, tumorigenicity, and the expression of stemness-related genes and epithelial to mesenchymal transition-related genes, whereas overexpression of SOX2 in SKOV3 or HO8910 ovarian cancer cells showed the opposite effects. In addition, we found that SOX2 expression was closely associated with chemo-resistance and poor prognosis in EOC patients. These results strongly suggest that SOX2 is required to maintain cancer stem cells in ovarian cancer. Targeting SOX2 in ovarian cancer may be therapeutically beneficial.