Immunoreactivities of androgen receptor, estrogen receptors, p450arom, p450c17 proteins in wild ground squirrels ovaries during the nonbreeding and breeding seasonsJournal of Ovarian Research - Tập 5 - Trang 1-10 - 2012
Xiaonan Li, Haolin Zhang, Xia Sheng, Ben Li, Jiao Zhou, Meiyu Xu, Qiang Weng, Gen Watanabe, Kazuyoshi Taya
The aim of this study was to elucidate the regulatory role of androgen in the follicular development of wild female ground squirrels. Immunohistochemical staining of FSHR, LHR, P450c17, P450arom, androgen receptor (AR), estrogen receptors (ERa and ERb) were executed in ovaries of female ground squirrels from both breeding and nonbreeding seasons. In addition, total ovarian proteins were extracted from the ovaries of squirrels from breeding and nonbreeding seasons, and Western blot analysis were performed in order to probe for FSHR, LHR, P450c17, P450arom, AR, ERa and ERb. The results of immunohistochemical staining and Western blotting of P450c17 showed that there was no significant difference between the breeding and nonbreeding seasons. It was found that granulosa cells expressed P450arom during the breeding season. In contrast, there was no positive staining of P450arom in the nonbreeding season. There was no significant difference in immunoreactivity of AR between the breeding and nonbreeding seasons. However, the immunoreactivities of ERa and ERb were both significantly reduced in the nonbreeding season compared to the breeding season. The positive stains of FSHR and LHR were found in the granulosa cells and theca cells of the ovaries of the breeding and nonbreeding seasons. In addition, the Western blotting results of FSHR and LHR showed a significant reduction in the nonbreeding season compared with the breeding season. These findings suggested that androgen might be predominantly converted into estrogen in order to regulate the follicular development via binding of estrogen receptors during the breeding season, whereas androgen might predominantly directly bind androgen receptor to regulate the follicular development during the nonbreeding season in the ovaries of wild female ground squirrels.
Next-generation sequencing-based genomic profiling analysis reveals novel mutations for clinical diagnosis in Chinese primary epithelial ovarian cancer patientsJournal of Ovarian Research - Tập 12 - Trang 1-10 - 2019
Lei Zhang, Min Luo, Hongying Yang, Shaoyan Zhu, Xianliang Cheng, Chen Qing
Ovarian cancer (OC) is one of the most malignant gynecological tumors, associated with excess death rate (50–60%) in ovarian cancer patients. Particularly, among newly occurred ovarian cancer patients, 70% of clinical cases are diagnosed at the advanced stage, which definitely delay the timely treatment and lead to high mortality rate within 5 years post diagnosis. Therefore, identification of sensitive gene markers, as well as development of reliable genetic diagnosis, are important for the early detection and precise therapy for OC patients. This study aims to identify novel genetic mutations and develop a feasible clinical approach for early OC diagnosis. The OC tissue-derived DNA sample was acquired from 31 OC patients, and the somatic gene mutations will be identified after comparison with normal samples, using Genome-wide analysis and next-generation sequencing. A total of 463 somatic mutations, which were considered as potential pathogenic sites, were assigned to 473 genes. Among them, 15 genes (TP53, TTN, MUC16, OR4N2, BRCA1, CAD, CCDC129, INSR, NAV3, NELL2, NRAS, OBSCN, PGLYRP4, RBM15B and TRPC7) were mutated on at least two sites. These genes were mapped to RNA sequencing (RNAseq) data, and a total of 117 genes had an absolute fold- change ≥ 2 and p ≤ 0.01. Five genes were mutated in at least two OC patients. Gene ontology (GO) classification indicated that a majority of genes participated in biological processes. Kyoto Enrichment of Genes and Genomes (KEGG) enrichment pathway analysis revealed that the genes were mainly involved in the regulation of metabolic signaling pathways. Taken together, this study identified several novel genetic alterations pathway for early clinical diagnosis and provided abundant information for understanding molecular mechanisms of the OC occurrence and development.
Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinomaJournal of Ovarian Research - Tập 16 - Trang 1-11 - 2023
Zheng Feng, Di Shao, Yuhang Cai, Rui Bi, Xingzhu Ju, Dongju Chen, Chengcheng Song, Xiaojun Chen, Jin Li, Na An, Yunjin Li, Qing Zhou, Zhihui Xiu, Shida Zhu, Xiaohua Wu, Hao Wen
Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population. We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients. The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p < 0.001; non-BRCA HRR: 88.6% vs 75.4%, p = 0.062). Patients with HRD status positive had significantly improved PFS compared with those with HRD status negative (median PFS: 30.5 months vs. 16.8 months, Log-rank p = 0.001). Even for BRCAwt patients, positive HRD was also associated with better PFS than the HRD-negative group (median: 27.5 months vs 16.8 months, Log-rank p = 0.010). Further, we found patients with pathogenic mutations located in the DNA-binding domain (DBD) of BRCA1 had improved FPS, compared to those with mutations in other domains. (p = 0.03). The HRD status can be identified as an independent significance in Chinese HGSOC patients treated with first-line platinum-based chemotherapy.
Ovarian seromucinous tumors: clinicopathological features of 10 cases with a detailed review of the literatureJournal of Ovarian Research - Tập 14 Số 1 - 2021
Romana Idrees, Nasir Ud Din, Sabeehudin Siddique, Saira Fatima, Jamshid Abdul‐Ghafar, Zubair Ahmad
Abstract
Background
The 2014 WHO Classification of ovarian neoplasms introduced a new entity of seromucinous tumors associated with endometriosis. These tumors encompassed a spectrum from benign to malignant and included seromucinous cystadenoma/ cystadenofibroma, seromucinous borderline tumor/atypical proliferative seromucinous tumor and seromucinous carcinoma. However, the 2020 WHO Classification of Female Genital Tumours removed seromucinous carcinomas as a distinct entity and recategorized them as Endometrioid carcinomas with mucinous differentiation. Here we describe clinico-morphologic features of seromucinous tumors recategorizing cases originally diagnosed as seromucinous carcinoma in light of 2020 WHO classification and present detailed review of literature.
Methods
Slides of seromucinous tumors were reviewed. Special emphasis was given to evaluation of stromal invasion. Follow-up was obtained.
Results
Ten cases were diagnosed. Mean age was 40 years. Four cases were bilateral. Mean size was 19 cm. Grossly; luminal papillary projections were seen in 6 cases. Tumors demonstrated a papillary architecture with papillae lined by stratified seromucinous epithelium showing nuclear atypia. Stromal invasion was seen in 4 cases. Six cases were reported as borderline seromucinous tumors and 4 cases originally diagnosed as seromucinous carcinoma were recategorized as endometrioid carcinoma with mucinous differentiation on review. Endometriosis was seen in 4 cases. CK7, PAX8 and ER were positive in 7/7 cases. Two cases showed extra-ovarian involvement. Follow up was available in 7 cases. Six patients were alive and well at follow up ranging from 8 to 46 months. Six patients received chemotherapy postoperatively. One patient with carcinoma died of disease 18 months postoperatively.
Conclusion
In our series, 4 cases were originally diagnosed as seromucinous carcinomas. However, these were recategorized in light of the 2020 WHO Classification of Female Genital tumors as endometrioid carcinomas with mucinous differentiation. Six cases were diagnosed as seromucinous borderline tumors. Thus, majority of cases were borderline in agreement with published literature.
Retrospective analysis of GnRH-a prolonged protocol for in vitro fertilization in 18,272 cycles in ChinaJournal of Ovarian Research - Tập 15 - Trang 1-11 - 2022
Lifeng Tian, Leizhen Xia, Qiongfang Wu
This large-cohort, retrospective study investigates the relationship between the number of oocytes retrieved and the clinical outcomes for patients receiving the GnRH-a prolonged protocol (mGnRH-a protocol) for fertilization in vitro or intracytoplasmic sperm injection–embryo transfer (IVF/ICSI-ET) treatment. We categorized 18,272 cycles into three groups by the number of oocytes retrieved (1–8, 9–17, and ≥ 18) during IVF with the GnRH-a prolonged protocol at the Reproductive Medical Center of Jiangxi Maternal and Child Health Hospital from January 2014 to December 2018 (excluding oocyte donation cycles), analyzing the associations among oocyte number and live birth rates (LBRs) or cumulative LBRs (CLBRs), as well as the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS). We defined the primary outcome as LBR and the secondary outcome to include the rate of patients at high risk for OHSS. The LBR (with fresh ET) per cycle of oocyte pick-up increased as the number of retrieved oocytes increased from 1 to ~ 8, plateaued between 9 ~ 17, and steadily decreased thereafter. However, the CLBR per cycle continued to increase as the oocyte number increased, as did the incidence of moderate-to-severe OHSS. Our results show a strong relationship between the number of oocytes retrieved and the CLBR following IVF treatment. The balance between treatment success and the risk of complications, especially OHSS, should be investigated further. We recommend a fresh-ET strategy for the GnRH-a prolonged protocol because the endometrial receptivity in the fresh cycles was better than those in the frozen cycles.
High EVI1 and PARP1 expression as favourable prognostic markers in high-grade serous ovarian carcinomaJournal of Ovarian Research - Tập 16 - Trang 1-13 - 2023
Paul Jank, Jonas Leichsenring, Svenja Kolb, Inga Hoffmann, Philip Bischoff, Catarina Alisa Kunze, Mihnea P. Dragomir, Moritz Gleitsmann, Moritz Jesinghaus, Wolfgang D. Schmitt, Hagen Kulbe, Christine Sers, Albrecht Stenzinger, Jalid Sehouli, Ioana Elena Braicu, Christina Westhoff, David Horst, Carsten Denkert, Stefan Gröschel, Eliane T. Taube
Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of protein expression of EVI1 alone and in combination with PARP1 and analyzed them in a cohort of patients with HGSOC. For 562 HGSOC patients, we evaluated EVI1 and PARP1 expression by immunohistochemical staining on tissue microarrays with QuPath digital semi-automatic positive cell detection. High EVI1 expressing (> 30% positive tumor cells) HGSOC were associated with improved progression-free survival (PFS) (HR = 0.66, 95% CI: 0.504–0.852, p = 0.002) and overall survival (OS) (HR = 0.45, 95% CI: 0.352–0.563, p < 0.001), including multivariate analysis. Most interestingly, mutual high expression of both proteins identifies a group with particularly good prognosis. Our findings were proven technically and clinically using bioinformatical data sets for single-cell sequencing, copy number variation and gene as well as protein expression. EVI1 and PARP1 are robust prognostic biomarkers for favorable prognosis in HGSOC and imply further research with respect to their reciprocity.
Effect of blastocyst morphology and developmental speed on transfer strategy for grade “C” blastocyst in vitrified‐warmed cyclesJournal of Ovarian Research - Tập 14 Số 1 - 2021
Yuxia He, Shiping Chen, Jianqiao Liu, Xiangjin Kang, Haiying Liu
Abstract
Background
High-quality single blastocyst transfer (SBT) is increasingly recommended to patients because of its acceptable pregnancy outcomes and significantly reduced multiple pregnancy rate compared to double blastocyst transfer (DBT). However, there is no consensus on whether this transfer strategy is also suitable for poor-quality blastocysts. Moreover, the effect of the development speed of poor-quality blastocysts on pregnancy outcomes has been controversial. Therefore, this study aimed to explore the effects of blastocyst development speed and morphology on pregnancy and neonatal outcomes during the frozen embryo transfer (FET) cycle of poor-quality blastocysts and to ultimately provide references for clinical transfer strategies.
Methods
A total of 2,038 FET cycles of poor-quality blastocysts from patients 40 years old or less were included from January 2014 to December 2019 and divided based on the blastocyst development speed and number of embryos transferred: the D5-SBT (n = 476), D5-DBT (n = 365), D6-SBT (n = 730), and D6-DBT (n = 467) groups. The SBT group was further divided based on embryo morphology: D5-AC/BC (n = 407), D5-CA/CB (n = 69), D6-AC/BC (n = 580), and D6-CA /CB (n = 150).
Results
When blastocysts reach the same development speed, the live birth and multiple pregnancy rates of DBT were significantly higher than those of SBT. Moreover, there was no statistical difference in the rates of early miscarriage and live birth between the AC/BC and CA/CB groups. When patients in the SBT group were stratified by blastocyst development speed, the rates of clinical pregnancy (42.44 % vs. 20.82 %) and live birth (32.35 % vs. 14.25 %) of D5-SBT group were significantly higher than those of D6-SBT group. Furthermore, for blastocysts in the same morphology group (AC/BC or CA/CA group), the rates of clinical pregnancy and live birth in the D5 group were also significantly higher than those of D6 group.
Conclusions
For poor-quality D5 blastocysts, SBT can be recommended to patients because of acceptable pregnancy outcomes and significantly reduced multiple pregnancy rate compared with DBT. For poor-quality D6, the DBT strategy is recommended to patients to improve pregnancy outcomes. When blastocysts reach the same development speed, the transfer strategy of selecting blastocyst with inner cell mass “C” or blastocyst with trophectoderm “C” does not affect the pregnancy and neonatal outcomes.
Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancerJournal of Ovarian Research - Tập 13 - Trang 1-10 - 2020
Hengyu Chen, Qingchun Deng, Wenwen Wang, Huishan Tao, Ying Gao
Cervical cancer is one of the most common female malignancy that occurs worldwide and is reported to cause over 300,000 deaths in 2018. Autophagy controls the survival and death of cancerous cells by regulating the degradation process of cytoplasm and cellular organelle. In the present study, the differentially expressed autophagy-related genes (ARGs) between healthy and cancerous cervical tissues (squamous cell neoplasms) were obtained using data from GTEx and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology (GO) as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Next, we conducted univariate Cox regression assay and obtained 12 ARGs that were associated with the prognosis of cervical cancer patients. We carried out a multivariate Cox regression analysis and developed six ARG-related prognostic signature for the survival prediction of patients with squamous cell cervical cancer (Risk score = − 0.63*ATG3–0.42*BCL2 + 0.85*CD46–0.38*IFNG+ 0.23*NAMPT+ 0.82*TM9SF1). Following the calculation of risk score using the signature, the patients were divided into high and low-risk groups according to the median value. Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis (P < 0.001). The value for area under the curves corresponding to the receiver operating characteristic (ROC) was 0.740. As observed, the expression of IFNG was negatively associated with lymph node metastasis (P = 0.026), while a high-risk score was significantly associated with increased age (P = 0.008). To further validate the prognostic signature, we carried out a permutation test and confirmed the performance of the risk score. In conclusion, our study developed six ARG-related prognostic signature for patients with squamous cell cervical cancer, which might help in improving the prognostic predictions of such patients.
