MiR-146a-5p and miR-191-5p are the Candidates for Novel Diagnostic Markers of Ovarian Clear Cell Carcinoma

Background: Ovarian cancer is a malignant gynecologic disease rarely diagnosed in the early stages. Among ovarian cancers, clear cell carcinoma has a poor prognosis due to its malignant potential. MicroRNAs (miRNAs) regulate gene expression in cells by suppressing the translation of the target gene or by degrading the target mRNA. They are also secreted from the cells in the blood, binding to the proteins or included in extracellular vesicles lipids and assisting in cell-cell communication. Hence, the serum miRNAs can also be diagnostic biomarkers for ovarian cancer. This study investigated and identified specific miRNAs for ovarian cancer clear cell carcinoma and compared them to those of the ovarian endometrioma in healthy controlpatients. Results: CA125, an ovarian tumor marker, did not differ between ovarian clear cell carcinoma, endometriosis, and healthy controlsthe three groups. Four miRNAs (miR-146a-5p, miR-191-5p, miR-484, and miR-574-3p) were analyzed. The miR-146a-5p and miR-191-5p expression levels were significantly increased in the serum samples from the ovarian clear cell carcinoma subjects compared to the healthy controlscontrols, but not in the subjects with endometriosis (P < 0.05). Furthermore, the bioinformatics analysis showed that CCND2 and NOTCH2 were the candidate target genes of miR‑146a-5p and miR-191-5p.Conclusions: Our results showed that miR‑146a-5p and miR-191-5p might be useful as an early and non-invasive diagnostic tool in ovarian clear cell carcinoma. These miRNAs can help in distinguishing between ovarian clear cell carcinoma and ovarian endometrioma. To the best of our knowledge, no studies have screened any candidates specifically for clear cell carcinoma.

The impact of lymphadenectomy on survival outcomes of ovarian clear cell carcinoma: a systematic review and meta-analysis

Background: The treatment strategies for ovarian clear cell carcinoma (OCCC) are the same as those for epithelial ovarian cancer. Due to the rarity of OCCC, no prospective studies of its surgery have been reported. Therefore, the therapeutic significance of lymphadenectomy for OCCC needs to be further clarified. Objectives: To assess the effectiveness of lymphadenectomy in patients with ovarian clear cell carcinoma by a meta-analysis. Search Strategy: The Web of Science, Scopus, PubMed, and other sources (e.g. Google Scholar) were searched from each database’s earliest inception to June 2021. Selection Criteria: English-language publications of observational studies that investigated the role of lymphadenectomy in patients with OCCC were included. Data Collection and Analysis: The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated. Main Results: The analysis demonstrated that lymphadenectomy is associated with significantly improved disease-specific survival (DSS) (HR=0.76; 95%CI=0.60-0.95; P=0.02; I2= 0.0%) and disease-free survival (DFS) (HR=0.58; 95%CI=0.33-1.00; P=0.05; I2=61%), but not for overall survival (OS) (HR=0.80; 95%CI=0.60-1.06; P=0.12; I2= 19%) and progression-free survival (PFS) (HR=0.95; 95%CI=0.64-1.42; P=0.79; I2= 0.0%). But it is worth noting that several single studies indicated a tendency of improved OS, PFS, DFS, DSS with lymphadenectomy. Conclusions: Lymphadenectomy could not significantly improve OS and PFS for OCCC, but is associated with improved DFS and DSS. Gynecologic oncologists should tailor treatment to patients to achieve optimal outcomes. And further studies are necessary to validate the impact of lymphadenectomy on OCCC. Keywords: ovarian clear cell carcinoma, lymphadenectomy, survival, systematic review, meta- analysis

Comparison of the Clinical Characteristics and Prognosis Between Clear Cell Carcinomas and High-grade Serous Ovarian Carcinomas

Objectives: To compare the clinical characteristics and prognosis of women with clear cell versus high-grade serous ovarian carcinoma.Methods: Retrospective analysis of the clinical data of 50 cases patients with ovarian clear cell carcinoma (OCCC) and 103 cases with high-grade serous ovarian carcinoma (HGSOC), who were initially treated and completed standardized therapy in Affiliated Hospital of Qingdao University from January 2013 to December 2017.Results: There were significant differences in age, gravidity (G > 1), chief complaint, with ovarian endometriosis, tumor diameter, unilateral or bilateral, cystic and solid tumor, CA125, HE4, CA199, lactate dehydrogenase (LDH), and FIGO stage between the two groups. The differences in the prognosis between OCCC patients and HGSOC patients with early stage (FIGO I-II) were not statistically significant. The 5-year overall survival and progression-free survival of OCCC patients were significantly worse than those of HGSOC patients with advanced stage (FIGO III-IV) (P < 0.05). FIGO stage and non-R0 resection were independent risk factors affecting the prognosis of patients with ovarian clear cell carcinoma, screening by Cox regression analysis. FIGO stage, the lowest value of CA125, and non-R0 resection were independent risk factors affecting the prognosis of patients with high-grade serous ovarian cancer.Conclusions: The clinical characteristics and prognosis of OCCC are different from those of HGSOC. OCCC patients have a significantly worse prognosis than those with HGSOC in the advanced stage (FIGO Ⅲ-Ⅳ). Satisfactory tumor resection is an essential factor related to the prognosis of patients with OCCC and HGSOC.

Comparison of Clinical Characteristics and Ultrasound Features of Ovarian Clear Cell Carcinoma and Ovarian High-Grade Serous Carcinoma

Purpose To investigate clinical and ultrasound features for differentiating ovarian clear cell carcinoma (OCCC) from ovarian high-grade serous carcinoma (HGSC). Methods Forty-five patients with OCCC and 72 patients with HGSC were retrospectively studied. Patient clinical characteristics and ultrasound features of tumors were evaluated. The differences, including laterality, menopausal status, Federation of Gynecology and Obstetrics (FIGO) stage between OCCC and HGSC patients were compared by Fisher’s exact test. The ultrasound features of tumors, including laterality, shape, configuration, color score, peritoneal implantation, and ascites, were evaluated and compared between the two groups. Results The average age at diagnosis in the OCCC group was 57.6±11.1 (range, 30–76) years, and 35.56% of patients were premenopausal. However, the average age at diagnosis was 63.4±12.2 (range, 42-81) years and 33.33% of patients were premenopausal in the HGSC group. There was a statistically significant difference in unilaterality (P< 0.001), clear boundaries (P<0.05), round or oval shape (P <0.05), and color score (P<0.05). Compared to HGSC patients, fewer OCCC patients had peritoneal implantation and ascites. There was a statistically significant difference in the mean size of papillary projections in OCCC and HGSC (P<0.05). The mean size of the papillary projections was significantly larger in OCCC than in HGSC. Conclusions OCCC commonly appeared as a large, round or oval mass with a clear boundary; the papillary projections of OCCC are larger and round. In contrast, HGSC was typically a large, irregular tumor with solid masses or mixed cystic-solid masses with small papillary projections.