Preoperative serum level of CA153 and a new model to predict the sub-optimal primary debulking surgery in patients with advanced epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to establish a preoperative model to predict the outcome of primary debulking surgery (PDS) for advanced ovarian cancer (AOC) patients by combing Suidan predictive model with HE4, CA125, CA153 and ROMA index. METHODS: 76 AOC Patients in revised 2014 International Federation of Gynecology and Obstetrics (FIGO) stage III-IV who underwent PDS between 2017 and 2019 from Yunnan Cancer Hospital were included. Clinical data including the levels of preoperative serum HE4, CA125, CA153 and mid-lower abdominal CT-enhanced scan results were collected. The logistics regression analysis was performed to find factors associated with sub-optimal debulking surgery (SDS). The receiver operating characteristic curve was used to evaluate the predictive performances of selected variables in the outcome of primary debulking surgery. The predictive index value (PIV) model was constructed to predict the outcome of SDS. RESULTS: Optimal surgical cytoreduction was achieved in 61.84% (47/76) patients. The value for CA125, HE4, CA153, ROMA index and Suidan score was lower in optimal debulking surgery (ODS) group than SDS group. Based on the Youden index, which is widely used for evaluating the performance of predictive models, the best cutoff point for the preoperative serum HE4, CA125, CA153, ROMA index and Suidan score to distinguish SDS were 431.55 pmol/l, 2277 KU/L, 57.19 KU/L, 97.525% and 2.5, respectively. Patients with PIV≥5 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing SDS were 73.7%, 82.9%, 62.9% and 72.3%, respectively. In the constructed model, the AUC of the SDS prediction was 0.770 (95% confidence interval: 0.654-0.887), P<0.001. CONCLUSION: Preoperative serum CA153 level is an important non-invasive predictor of primary SDS in advanced AOC, which has not been reported before. The constructed PIV model based on Suidan's predictive model plus HE4, CA125, CA153 and ROMA index can noninvasively predict SDS in AOC patients, the accuracy of this prediction model still needs to be validated in future studies.

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial.

PURPOSE: This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS: Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS: Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION: Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

Erratum: Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer.

[This corrects the article on p. 38 in vol. 6, PMID: 27073721.].

WD repeat and SOCS box containing protein 2 in the proliferation, cycle progression, and migration of melanoma cells.

BACKGROUND: WD repeat and SOCS box containing protein (WSB) molecules have important roles in tumorigenesis. WSB1 is dysfunctional in many malignancies. However, the effects of WSB2 in tumors, including melanoma, have not been reported. Here, we investigated the effects of WSB2 in melanoma cell proliferation, cycle progression, and migration, and the underlying mechanisms. METHODS: First, WSB2 expression levels and their association with clinicopathological features were evaluated in human melanoma tissue samples. Then, WSB2 was knocked down, using specific shRNA, in melanoma A375 and G361 cells. Proliferation, cycle progression, and migration of A375 and G361 cells were evaluated by 3-(4,5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-etrazolium, inner salt (MTS), colony formation, 5-ethynyl-2'-deoxyuridine (EdU), cycle, and transwell assays. The effects of WSB2 knockdown on melanoma in vivo were determined using a xenograft mouse model. To investigate the underlying mechanisms, levels of c-Myc, ß-catenin, phosphorylated retinoblastoma (p-Rb), cyclin-dependent kinase 4 (CDK4), and Cyclin D3 proteins were determined by western blotting in melanoma A375 cells with WSB2 knocked down. Furthermore, ß-catenin agonism, SKL2001, was used to evaluate the mechanisms by which knockdown of WSB2 regulated cell proliferation. RESULTS: WSB2 levels were high and they were associated with clinicopathological features in patients with melanoma. shRNA-mediated knockdown of WSB2 could inhibit proliferation, both in vivo and in vitro. Cycle progression and migration of A375 and G361 cells were also significantly inhibited by WSB2 knockdown. Moreover, down-regulation of WSB2 decreased the levels of c-Myc, ß-catenin, p-Rb, Cyclin-dependent kinase 4 (CDK4), and Cyclin D3 in melanoma G361 cells with WSB2 knocked down. Moreover, SKL2001 could effectively rescue WSB2 knockdown-mediated inhibition of cell proliferation in melanoma. CONCLUSION: This is the first report to demonstrate the effects of WSB2 on melanoma cell function. WSB2 has potential to become a new therapeutic target in patients with melanoma.

Clinical value of combined detection of miR-1202 and miR-195 in early diagnosis of cervical cancer.

The clinical value of the combined detection of miR-1202 and miR-195 in the early diagnosis of cervical cancer was studied. A retrospective analysis of 70 cervical cancer patients treated in the The Third Affiliated Hospital of Kunming Medical University and Yunnan Cancer Hospital from October 2015 to December 2017 was performed, and the lesion tissues were used as the experimental group. Normal cervical tissues from another 67 healthy females confirmed by physical examination at the same period were selected as the control group. The FIGO staging criteria were used for staging of the cervical cancer patients, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method was used for the detection of the expression of miR-1202 and miR-195 in different tissues, and the receiver operating curve (ROC) was used for the analysis of the application values of miR-1202 and miR-195 diagnosis alone and their combined diagnosis in early cervical cancer patients. The levels of miR-1202 and miR-195 in the experimental group were lower than those in the control group (P<0.05). The differences were significant in the different stages of cervical cancer tissues (P<0.05). The later the staging of cervical cancer tissues were, the lower the levels of miR-1202 and miR-195 were. The sensitivities and area under the curve (AUC) values of miR-1202 and miR-195 in the combined diagnosis of early cervical cancer were significantly higher than those of miR-1202 and miR-195 alone. The expression levels of miR-1202 and miR-195 in the cervical cancer patients are different in different stages. Guiding clinical treatment and prognosis according to the results of combined detection is beneficial for the development of treatment for cervical cancer patients and for prognostic judgement, worthy of popularization and application.

CT of ovarian cancer: 3D cinematic rendering for preoperative evaluation.

BACKGROUND: Ovarian cancer is the second most common gynecologic malignancy. As the primary imaging modality, computed tomography (CT) can provide staging information for preoperative planning and determination of surgical resectability. As a new three-dimensional postprocessing tool for CT images, cinematic rendering (CR) has the potential to depict anatomic details accurately. CASE PRESENTATION: (Case 1) A 44-year-old married woman was diagnosed with recurrent ovarian cancer. CT images indicated the recurrent nodules and masses in the pelvic cavity and the upper middle abdominal peritoneum. The CR image showed that the multiple metastatic lesions and lymph nodes could not be completely removed by reoperation. The patient agreed to receive continued chemotherapy. (Case 2) A 51-year-old woman was admitted to our hospital due to abdominal distension and defecation that had increased for 6 months, with aggravation over the past 3 days. CT examination found cystic and solid masses in the bilateral ovarian area. The CR image demonstrated that the ovarian mass violated the posterior wall of the bladder and the anterior rectal wall. The preoperational imaging evaluation ensured the safety of the operation. CONCLUSION: CR could improve the visualization of ovarian cancer masses, metastatic lymph nodes, and peritoneal metastases. CR has a good clinical value and will be more helpful in the preoperational evaluation of ovarian cancer.

Elevated expression of flotillin-1 is associated with lymph node metastasis and poor prognosis in early-stage cervical cancer.

Accumulating evidence has revealed that the expression of the lipid raft protein flotillin-1 is elevated in various human cancers, but the role flotillin-1 plays in the carcinogenesis of cervical cancer remains unclear. The expression profile of flotillin-1 was assayed using real-time PCR, western blotting, and immunohistochemical (IHC) staining in cervical cancer cell lines and cancer tissues with paired adjacent noncancerous cervical tissues. The expression of flotillin-1 protein was detected by IHC staining in a large cohort of 308 paraffin-embedded cervical cancer tissues. Ectopic expression and the short hairpin RNA interference approach were employed to determine the role of flotillin-1 in cervical cancer cell metastasis and the possible mechanism involved. Flotillin-1 expression protein and mRNA were significantly upregulated in cervical cancer cell lines and cancer tissues; elevated expression of flotillin-1 protein in early-stage cervical cancer was significantly associated with pelvic lymph node metastasis (P < 0.001), and was an independent predictive factor of poor overall survival. Moreover, flotillin-1 up- and downregulation remarkably affected cervical cancer cell motility and invasion, respectively, through epithelial-mesenchymal transition (EMT) regulated by the Wnt/ß-catenin and nuclear factor-κB (NF-κB) pathways. Our results suggest that flotillin-1 facilitates cervical cancer cell metastasis through Wnt/ß-catenin and NF-κB pathway-regulated EMT and that the flotillin-1 expression profile serves not only as novel predictor of pelvic lymph node metastasis, but also as neoteric risk factor for patients with early-stage cervical cancer.