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Emerging studies have demonstrated the promising clinical value of circulating tumor cells (CTCs) for diagnosis, disease assessment, treatment monitoring and prognosis in epithelial ovarian cancer. However, the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common standards.We enrolled 160 patients with epithelial ovarian cancer as the experimental group, and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control group. We enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens (EpCAM and MUC1), and used multiple reverse transcription-polymerase chain reaction (RT-PCR) detecting three markers (EpCAM, MUC1 and WT1) for quantification. And then we used a binary logistic regression analysis and focused on EpCAM, MUC1 and WT1 to establish an optimized CTC detection model.The sensitivity and specificity of the optimized model is 79.4% and 92.2%, respectively. The specificity of the CTC detection model is significantly higher than CA125 (92.2%Our study presents an optimized detection model for CTCs, which consists of the expression levels of three markers (EpCAM, MUC1 and WT1). In comparison with CA125, our model has high specificity and demonstrates better diagnostic values, especially for early-stage ovarian cancer. Detection of CTC

Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT are still under investigation. In this study, we identified a previously unrecognized role of HSP90 in cooperating with signal transducer and activator of transcription 3 (STAT3) to regulate TWIST1 transcription in cancer cells. The HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin suppressed TWIST1 mRNA expression and promoter activity in epithelial ovarian cancer, renal clear cell cancer, and nasopharyngeal cancer cell lines. The interactions between HSP90 and transcription factors were visualized in cancer cell lines and tumor tissues using proximity ligation assays. Our findings reveal that HSP90 promotes the binding of STAT3 to the TWIST1 promoter, leading to the transcription of TWIST1. The inhibition of HSP90 downregulates STAT3 activity and TWIST1 transcription, thereby suppressing EMT and potentially inhibiting tumor progression, metastasis, and chemoresistance in different types of cancers. SIGNIFICANCE STATEMENT: Our study provides new evidence that HSP90 promotes EMT through enhancing TWIST1 transcription, which can be suppressed by HSP90 inhibitors. The HSP90 inhibitor inhibits EMT, thus potentially slowing down tumor growth, invasion, dissemination, metastasis, and drug resistance. These findings will hopefully pave the way for new therapeutic opportunities to target EMT and metastasis using HSP90 inhibitors.

Introduction/Background To compare the chemoresistance and survival in patients with stage IIIC or IV epithelial ovarian cancer (EOC) who were treated with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) or primary debulking surgery (PDS). The clinical characteristics of patients who benefited from NACT were further evaluated. Methodology We retrospectively analyzed 220 patients who underwent NACT followed by IDS or PDS from January 2002 to January 2017 treated at Peking University Third Hospital. Differences in clinicopathological features, chemoresistance and prognosis were analyzed. Results The incidence rate for optimal cytoreduction and chemoresistance in the NACT group was relatively higher than those in PDS group. No differences were observed in progression free survival (PFS) or overall survival (OS). Patients without macroscopic RD in the NACT group (NACT-R0) had a similar prognosis compared to patients in the PDS group who had RD Conclusion Patients without RD after PDS had the best prognosis, whereas patients with RD after NACT followed by IDS had the worst. However, even if patients achieved no RD, their prognosis varied depending on chemosensitivity. Survival was better in patients who were chemosensitive compared to patients who underwent PDS but had macroscopic RD. Hence evaluating the chemosensitivity and feasibility of complete cytoreduction in advance is crucial. Disclosure Nothing to disclose.

As a mismatch repair (MMR) gene, hMLH1 plays an important role in the maintenance of chromosomal integrity. Several studies have investigated the associations of hMLH1 -93GA (rs1800734) and Ile219Val (rs1799977) in diverse tumor types with discordant results, but their roles in ovarian cancer in the Chinese population remains to be elucidated.In a case-control analysis, we assessed the association between these two polymorphisms and ovarian cancer risk in 421 ovarian cancer patients and 689 control subjects in the Chinese population using logistic regression.We found that the variant hMLH1 genotypes (-93AA and AG) are associated with risk of ovarian cancer (adjusted odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.42-2.89) compared with the -93GG genotype. The A allele increases the risk of ovarian cancer in a dose-dependent manner (P10-4). Functional test showed that -93A allele increased hMLH1 promoter transcriptional activity and the luciferase activity. However, no significant difference was found in the genotype frequencies at the Ile219Val site between the cases and controls.These findings indicate that the -93GA polymorphism in hMLH1 may affect ovarian cancer susceptibility in the Chinese population.

Additional file 8: Table S6. Univariate analysis of risk factors for OS after NACT-IDS and PDS. (DOCX 19 kb)

// Huamao Liang 1 , Hongyan Guo 1 , Chunyu Zhang 1 , FuLi Zhu 1 , Yu Wu 1 , Kun Zhang 1 , Hua Li 1 and Jinsong Han 1 1 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, P.R. China Correspondence to: Hongyan Guo, email: bysyghy2016@163.com Keywords: ovarian cancer, epithelial, laparoscopy, cytoreductive surgery, primary Received: January 12, 2017 Accepted: October 02, 2017 Published: November 03, 2017 ABSTRACT Objectives: To assess the feasibility and outcome of primary laparoscopic cytoreductive surgery on advanced epithelial ovarian cancer in comparison with conventional open surgery. Materials and Methods: Patients undergoing primary laparoscopic cytoreductive surgery (LCS) from March 2007 to December 2016 were matched to controls treated with laparotomic cytoreduction during the same period. Procedural data and outcomes were analyzed. Results: The LCS group ( n = 64) and laparotomic group ( n = 68) had similar age, BMI, stages, histologic type and grading. The LCS group exhibited significantly less operating time ( P < 0.001), less intraoperative blood loss ( P < 0.001), and shorter time to recover postoperatively ( P = 0.002). No statistical difference was observed for the number of pelvic and para-aortic lymph nodes dissected ( P = 0.326 and P = 0.151). Significant difference was observed in satisfaction of the cytoreduction (95.3% vs. 76.5%, P = 0.008). No significant difference were observed either in intra-operative or in post-operative complications between the two groups ( P = 0.250). Three patients in the LCS group experienced intra-operative complications (4.7%) and were all treated laparoscopically. The conversion rate was 3.1%. No significant differences were observed in the progression-free survival and overall survival between the two groups during the medium follow-up of 18 months ( P = 0.236 and P = 0.216). The 2-year and 3-year progression-free survival was 67.9%, 55.5% in LCS group and 53.8%, 33.3% respectively in the control group. The 2-year and 3-year overall survival was 95.8%, 88.7% respectively in the LCS group and 89.0%, 83.7% in the control group. Conclusions: Primary laparoscopic cytoreductive surgery in some strictly selected advanced stages of EOC patients was feasible and safe, resulting in oncologic outcomes not inferior to those in open surgery.