Identification of MAD2L1 and BUB1B as Potential Biomarkers Associated with Progression and Prognosis of Ovarian Cancer.

Ovarian cancer develops insidiously and is frequently diagnosed at advanced stages. Screening for ovarian cancer is an effective strategy for reducing mortality. This study aimed to investigate the molecular mechanisms underlying the development of ovarian cancer and identify novel tumor biomarkers for the diagnosis and prognosis of ovarian cancer. Three databases containing gene expression profiles specific to serous ovarian cancer (GSE18520, GSE12470, and GSE26712) were acquired. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were analyzed for the differentially expressed gene (DEGs). The protein-protein interaction (PPI) network was constructed using the STRING database. The pivotal genes in the PPI network were screened using the Cytoscape software. Survival curve analysis was performed using a Kaplan-Meier Plotter. The cancer genome atlas and Gene Expression Omnibus databases were used to find the relationship between Hub gene and serous ovarian cancer. PCR and immunohistochemistry were used to detect the expression of Hub gene in serous ovarian cancer tissues and cells. Downstream pathways of the candidate tumor marker genes were predicted using Gene Set Enrichment Analysis. In this study, 252 DEGs were screened for pathway enrichment. 20 Hub genes were identified. Survival analysis suggested that Aurka, Bub1b, Cenpf, Cks1b, Kif20a, Mad2l1, Racgap1, and Ube2c were associated with the survival of patients with serous ovarian cancer. MAD2L1 and BUB1B levels were significantly different in serous ovarian cancer at different stages. Finally, Mad2l1 was found to play a role in the cell cycle, oocyte meiosis, and ubiquitin-mediated proteolysis. Meanwhile, Bub1b may play a role in the cell cycle, ubiquitin-mediated proteolysis, and spliceosome processes. Mad2l1 and Bub1b could be used as markers to predict ovarian carcinogenesis and prognosis, providing candidate targets for the diagnosis and treatment of serous ovarian cancer.

Can serum ferritin serve as a biomarker for the prognosis of gynecological malignant tumors? A retrospective cohort study.

PURPOSE: It is widely accepted that there is a strong relationship between iron levels and cancer. This study aimed to investigate the relationship between serum ferritin levels and the severity and prognosis of gynecological malignant tumors. METHODS: This retrospective study included patients with gynecological malignant tumors at Sir Run Run Shaw Hospital in the Department of Obstetrics and Gynecology from January 2013 to June 2019. Patients were grouped according to their serum ferritin level: low (< 13 µg/L), normal (13-150 µg/L), and high (> 150 µg/L). Correlation analyses were performed between serum ferritin level and other factors. Cox univariable and multivariable analysis and Kaplan-Meier survival curves were used to assess the impact of ferritin on survival in patients with gynecologic tumors. RESULTS: The 402 total patients were divided into a low (n= 37), normal (n= 182), and high (n= 183) ferritin level group. Correlation analyses were performed that WBC, MCV, CRP, CA125, and CA153 were significantly positively correlated with serum ferritin level. The Kaplan-Meier survival curves revealed that of the three groups analyzed, the high serum ferritin level group had a significantly shorter survival time versus the normal and low serum ferritin level groups (log-rank P= 0.003). Univariable Cox regression analysis identified that patients with high serum ferritin levels had a significant correlation with risk of death compared to the patients with lower and normal serum ferritin levels. Serum ferritin was not found to be significant (HR = 0.792, 95% CI: 0.351-1.787, P= 0.574) in the multivariable Cox analysis. CONCLUSION: Although this study did not find serum ferritin to be a significant independent prognosis indicator in gynecological malignant tumors, this study did identify that gynecological malignant tumor patients with high serum ferritin levels have significantly less survival time than patients with low or normal serum ferritin levels.

Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency.

Objective: We explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI. Methods: Fecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman's rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage. Results: The abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-ß1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-ß1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice. Conclusions: The interactions between the gut microbiota, serum metabolites, and serum TGF-ß1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-ß1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

Evaluation of cervical length and optimal timing for pregnancy after cervical conization in patients with cervical intraepithelial neoplasia: A retrospective study.

To evaluate the change of cervical length and the best timing for pregnancy after cervical conization in patients with cervical intraepithelial neoplasia (CIN).This was a retrospective study including patients under 40 years with fertility desire treated by cervical conization for CIN. To assess the cervical length, the patients were divided into 2 groups according to different surgery procedure: loop electrosurgical excision procedure (LEEP) and cold knife conisation (CKC). Patients with cervical length < 2.5 cm in CKC group were divided into 2 groups according to whether receiving cervical cerclage. Trans-vaginal ultrasound examination was used to measure cervical length by fixed professional sonographers.In LEEP group, the cervical length preoperative was significantly longer than 3 months postoperatively (3.03 ±â€Š0.45 cm vs 2.84 ±â€Š0.44 cm, P = .000). In CKC group, the cervical length preoperative was significantly longer than 3 and 6 months postoperatively (2.90 ±â€Š0.41 cm vs 2.43 ±â€Š0.43 cm and 2.68 ±â€Š0.41 cm, respectively, P = .000). Cervical length was significantly longer at 12 and 9 months after cerclage compared to that without cerclage. Eighteen patients got pregnant in LEEP group, among which one was pregnant at 5 months postoperatively and had premature delivery. There was 1 inevitable abortion and 1 preterm birth among 39 pregnant patients from CKC group.Patients who have fertility desire with CIN were recommended for pregnancy at 6 and 9 months after LEEP and CKC, respectively. Cerclage effectively prolonged cervical length in patents with that less than 2.5 cm to prevent cervical incompetence.

Changes of Intestinal Microbiota in Ovarian Cancer Patients Treated with Surgery and Chemotherapy.

PURPOSE: Ovarian cancer is the leading cause of death in gynecologic malignancies. Growing evidences demonstrate that a complicated relationship exists between the gut microbiota and cancer treatment. However, there are few studies explored the alterations of gut microbiota in ovarian cancer patients following anti-cancer treatments. Therefore, we aim to analyze the changes of the gut microbiota in ovarian cancer patients treated with radical surgery and chemotherapy. PATIENTS AND METHODS: The microbial genes were examined from a total of 75 fecal samples from 18 ovarian cancer patients, including 10 preoperative fecal samples (Group B), 4 postoperative fecal samples (Group M0), as well as 61 fecal samples after first to fifth cycles of chemotherapy, using 16S rRNA sequencing. RESULTS: Our results showed that fecal samples collected in postoperative (Group M0) exhibited significant decreases in abundance of Bacteroidetes and Firmicutes, while a significant increase in abundance of Proteobacteria compared with preoperative (Group B) fecal samples. LEfSe analysis identified that Bilophila and Faecalibacterium are the key genera in Group B, while Klebsiella and Enterococcus are the key genus in Group M0. Compared with before chemotherapy, the abundance of Bacteroidetes and Firmicutes increased, and the abundance of Proteobacteria decreased after chemotherapy. In addition, anaerobic bacteria, such as Bacteroides, Collinsella and Blautia, exhibited significant increases after chemotherapy. Moreover, we observed that certain bacterial genera were significantly correlated with clinicopathological characteristics of ovarian cancer patients. CONCLUSION: Our study suggested that radical surgery and chemotherapy altered the composition of gut microbiota in ovarian cancer patients. Therapeutic strategies targeting the gut microbiota may be beneficial for the clinical treatment of ovarian cancer.

WTAP is a prognostic marker of high-grade serous ovarian cancer and regulates the progression of ovarian cancer cells.

BACKGROUND: The Wilms' tumor suppressor WT1 is reported to work in a range of physiological processes at both transcriptional and posttranscriptional level. WT1-associating protein (WTAP), a nuclear protein co-localized with splicing factors, also plays a vital role in cellular function and cancer progression. However, little is known about the role of WTAP in ovarian cancer and the underlying mechanism. MATERIALS AND METHODS: To evaluate the expression of WTAP, multiple means were applied in clinical tissues, including immunohistochemistry, quantitative reverse transcriptase PCR (qRT-PCR), and Western blot. Two representative ovarian cancer cell lines (3AO and SKOV3) were used to assess the malignant influence of WTAP on proliferation, apoptosis, and migration. To explore its function, WTAP was additionally down-regulated by lentivirus. RESULTS: High expression of WTAP in high-grade serous ovarian carcinoma (HGSOC) predicted a shorter overall survival (P<0.01). Furthermore, WTAP expression was higher in HGSOC, compared with that in normal ovary group (P<0.01), benign ovarian tumor group (P<0.01), and non-HGSOC group (P<0.05). In HGSOC, high expression of WTAP was significantly related with the lymph node metastasis (P<0.05). In ovarian cancer cell lines, cell proliferation and migration were considerably reduced after WTAP was down-regulated, while apoptotic rate was increased. Moreover, the effect of WTAP in 3AO and SKOV3 might be relevant with MAPK and AKT signaling pathways. CONCLUSION: WTAP is highly expressed in HGSOC, and indicates a worse survival outcome. Therefore, it is highly possible that WTAP has a prognostic implication in the patients of HGSOC. In addition, WTAP down-regulation also plays a tumor suppressor role in 3AO and SKOV3 cell lines.

SNHG15: a promising cancer-related long noncoding RNA.

Cancer is expected to rank as the leading cause of death worldwide due to increasing morbidity and mortality. Long noncoding RNAs (lncRNAs) have been found to play pivotal roles in multiple biological processes, such as transcriptional interference, posttranscriptional regulation and epigenetic modification. Small nucleolar RNA host gene 15 (SNHG15), a snoRNA host gene which produces a short half-lived lncRNA, was reported to be upregulated in tumor cells and participate in the occurrence and development of multiple cancers. And more than half of the SNHG15 research in cancers has been published within the last 2 years. In this review, we summarized the current evidence concerning the biological functions and molecular mechanisms of SNHG15 in various cancers, including gastric, hepatocellular, pancreatic, colorectal, breast, and thyroid cancer, osteosarcoma, glioma, lung cancer, renal cell carcinoma, and epithelial ovarian cancer. SNHG15 plays critical roles in regulation of cell proliferation, migration and invasion of tumors via different potential mechanisms. Moreover, the abnormal expression of SNHG15 was associated with clinical features of patients with cancers. Consequently, SNHG15 could be considered as a promising biomarker for cancer diagnosis, prognosis or treatment.

Short-term recurrence and distant metastasis following robotic-assisted radical hysterectomy with pelvic lymphadenectomy and chemoradiotherapy for a stage IB1 cervical adenocarcinoma: A case report and literature review.

RATIONALE: Postoperative concurrent chemoradiotherapy (CCRT) is considered the standard treatment for patients with early stage cervical cancer with positive pelvic nodes, yet many patients with high-risk factors treated with CCRT still suffered from distant metastasis. PATIENT CONCERNS: A 48-year-old woman presented with abnormal vaginal bleeding for 5 months. Thin prep liquid-based cytology test revealed low-grade squamous intraepithelial lesion and the human papillomavirus test (type 58) was positive. Magnetic resonance imaging showed a mass measuring 17 × 15 mm, located predominantly in the posterior lip of uterine cervix. Colposcopy biopsy reported adenocarcinoma of the cervix. DIAGNOSIS: Cervical adenocarcinoma stage IB1. INTERVENTIONS: A robotic-assisted radical hysterectomy with pelvic lymphadenectomy was performed followed by postoperative CCRT. OUTCOMES: Distant metastasis was occurred shortly after postoperative CCRT and the patient died 9 months from initial diagnosis. LESSONS: In cases of new nodule in bones, lower abdominal distension and bloating occurring shortly after CCRT in early stage cervical adenocarcinoma, clinicians should bear in mind that recurrence should be considered. Development of more effective treatment to improve the survival outcomes of patients with postoperative metastasis is needed.