Objective:This study aims to assess the long-term incidence risk of gynecologic malignancy in postmenopausal women presenting with vaginal bleeding and pathologically confirmed benign endometrial lesions, and to screen for clinical independent risk factors to provide evidence for risk stratification and follow-up management of this population. Methods:We conducted a retrospective cohort study of 696 postmenopausal women presenting with vaginal bleeding who underwent diagnostic endometrial curettage. Histopathological evaluation established the initial diagnosis; patients with initially benign endometrial pathology underwent short-term (3-month) histologic re-evaluation, and eligible individuals were enrolled in long-term clinical follow-up. We compared the distribution of pathological subtypes between initial and follow-up diagnoses and performed univariate Cox regression and multivariate Cox proportional hazards regression analyses to identify independent predictors of gynecologic malignancy. Results:The initial diagnosis rates of endometrial malignancy and precancerous lesions were 15.1% (105/696) and 2.9% (20/696), respectively. Among the 118 patients with initially benign endometrial pathology, 5.1% (6/118) and 7.6% (9/118) were diagnosed with malignancy and precancerous lesions, respectively, within 3 months of initial evaluation. Of the 453 patients eligible for long-term follow-up, 338 completed follow-up (25.4% lost to follow-up), during which 16 incident malignancies and 8 incident precancerous lesions were identified. High-grade serous carcinoma constituted a significantly higher proportion of malignancies detected during follow-up (43.8%) than of those diagnosed initially (6.5%; P < 0.001). Patients with high-grade serous carcinoma had a significantly lower BMI compared with those with endometrioid adenocarcinoma or precancerous lesions (P = 0.008); however, median diagnostic delay did not differ significantly across histologic subtypes (P = 0.850). Univariable Cox regression identified RDW, endometrial thickness, and age as factors associated with the risk of subsequent neoplasia. Multivariable Cox proportional hazards regression analysis confirmed baseline red blood cell distribution width (HR = 1.331, 95% CI: 1.086-1.630, P = 0.009) and endometrial thickness (HR = 4.452, 95% CI: 2.111-9.391, P < 0.001) as independent predictors of gynecologic malignancy. Conclusion:Our findings confirm that postmenopausal women with vaginal bleeding and initial benign endometrial lesions carry higher long-term gynecologic malignancy risk. Given their poor tumor prognosis, standardized screening and long-term surveillance are clinically vital for this high-risk cohort.

Ovarian endometriosis (OEM) is characterised by ectopic endometrial tissue growth within the ovary. In these ectopic lesions, the ectopic epithelium plays a crucial role in OEM progression and has been associated with malignant transformation in a subset of cases. However, conventional histology limits understanding of ectopic epithelial distribution, structure, and its perivascular microenvironment, thus impeding pathogenesis studies. To address this, we employed a modified tissue-clearing method and  three-dimensional (3D) imaging to systematically characterise OEM, revealing key, previously unreported spatial characteristics. We found significantly higher densities of ectopic epithelium and vasculature in the outer cystic wall versus the inner. Furthermore, our method improved the detection rate of ectopic epithelium and revealed its morphological polymorphism at both tissue and cellular levels. Besides, we demonstrated that vessels preferentially cluster around ectopic epithelium, with their distribution pattern strongly linked to the location of ectopic epithelium. Strikingly, we observed endometrial-like structures in lesional vasculature in 3 of 49 cases, representing a novel morphological observation that warrants further investigation. This study significantly advances our understanding of OEM histopathology, offering insights for clinical diagnosis and treatment.

PurposeThis study aims to explore the predictive value of baseline platelet count and its morphological indicators for the prognosis of ovarian cancer patients.MethodA retrospective cohort study was conducted at a gynecological oncology center in Beijing, involving ovarian cancer patients between 2011 and 2022 and followed up until December 2024. Data were extracted from clinical information system. The primary endpoints were recurrence; the primary indicator was progression-free survival during the follow-up period.ResultA total of 265 patients was included in this study. During the follow-up period, 110 patients recurred, whereas 155 patients achieved remission. Univariate analysis revealed that baseline platelet count was associated with progression-free survival. The stratified analysis presented a U-shaped curve by smooth curve fitting. Threshold effect analysis indicated that the inflection points of the U-shaped curve occurred at platelet count of 236×109/L (95% CI 222-256×109/L), the lowest risk of recurrence. The U-shaped curve was confirmed by Multinomial logistic regression (P < 0.005). The relationship between platelet morphological indicators and recurrence risk is modulated by the level of baseline platelet count(P < 0.05). In the third tertile of platelet distribution, morphological indicators are associated with recurrence risk and exhibit a protective effect; however, in patients with high-grade serous carcinoma and at different clinical stages, recurrence risk is not significantly associated with morphological indicators; but morphological indicators still have a protective effect on other pathological types (PDW, OR 0.6, P = 0.017; MPV, OR 0.3, P = 0.025; PLCR, OR 0.9, P = 0.022,respectively). The non-parametric Mann-Whitney U test also showed that the predictive value of baseline platelet morphology indicators for recurrence risk was only demonstrated in patients with other pathological types.ConclusionThis study reveals a significant nonlinear association between platelet count and morphology and the risk of recurrence of ovarian cancer. Exploring the complex mechanisms linking baseline platelet characteristics to the prognosis of ovarian cancer will help facilitate the application of platelets as meaningful prognostic indicators and therapeutic targets in clinical practice.

Persistent human papillomavirus (HPV) infection is a key risk factor for cervical cancer, often associated with changes in the vaginal microbiome (VMB). High-throughput 16S rRNA sequencing was used to study the VMB in a prospective cohort of 731 individuals. Participants were monitored through two follow-up screenings and then categorized into two groups: 22 female patients with persistent HPV infection (PHI), 31 female patients who cleared the infection (HC). After excluding those with HPV and other urogenital infections, 43 female patients were selected as controls, and their samples were analyzed using the same high-throughput sequencing method. Results indicate that high-risk HPV infections correlate with increased microbial diversity and reduced Lactobacillus levels. Even after HPV clearance, distinct microbial differences persist, suggesting that VMB could serve as a biomarker for monitoring infection and cervical health management, especially in populations at higher risk.

Objective To study immediate therapeutic outcomes, subsequent fertility effects and menstrual changes in cesarean scar pregnancy patients who received uterine artery embolization with or without methotrexate followed by ultrasound guided curettage. Materials and methods Totally, 82 patients who met the inclusion criteria were enrolled in our study and divided into two groups. Group I included 50 patients who received uterine artery embolization and ultrasound guided curettage, and Group II had 32 patients who received uterine artery embolization plus methotrexate and ultrasound guided curettage. Results No significant difference was found in demographic features between the two groups, but the level of serum β-human chorionic gonadotropin before uterine artery embolization, 1 day and 7 days after ultrasound guided curettage is significantly higher in Group II than that in Group I. Patients were followed up for a mean time of 38.9 months. 10 patients had reproductive desire and half of them failed while half succeeded including one recurrent cesarean scar pregnancy. Most patients (74.4 %) had no menstrual changes, while 19 patients complaint a decrease in menstruation and 2 patients had a prolonged menstruation. Conclusion Uterine artery embolization combined with or without methotrexate plus ultrasound guided curettage is an effective, safe and recommended therapy to eliminate the gestational sac and meanwhile to preserve fertility for cesarean scar pregnancy patients, and methotrexate could help reduce the blood level of β-human chorionic gonadotropin and shorten the days to recover to normal, thus reducing hospitalized days.

BACKGROUND:Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects multiple organs throughout the body, which puts chemotherapy patients at even greater risk. This study aims to identify the clinical characteristics of gynecological cancer patients infected with SARS-CoV-2 during chemotherapy. METHODS:Gynecological cancer patients infected with SARS-CoV-2 during chemotherapy from August 1, 2022, to January 31, 2023, were enrolled in this observational cohort study. Patients in the control group were not infected with SARS-CoV-2. All continuous variables, including blood cells (leukocytes, neutrophils, lymphocytes) and biochemical indices (alanine transaminase (ALT), Aspartate transferase (AST), lactate dehydrogenase (LDH), albumin and creatinine) were repeatedly measured and analyzed statistically by the generalized additive mixed model (GAMM). Latent class analysis was estimated for the high-risk factors of severe COVID-19. The primary outcome was to develop a severe condition. RESULTS:During the study period, there were 71 patients with chemotherapy in our center. Of the 57 cases infected with SARS-CoV-2, 14 patients without infection, the infection rate was 80.28%. 52 cases out of the 57 infected patients were included in this study, 9.62% (5/52) cases showed severe disease, and 1 patient died. 51 cases survived during the acute coronavirus disease 2019 (COVID-19) phase. If chemotherapy is given after SARS-CoV-2 infection, tissues and organs that are sensitive to chemotherapy are more likely to be re-damaged by COVID-19. The plasma levels of leukocytes, neutrophils, lymphocytes, ALT, and AST decreased; LDH and creatinine in plasma showed a linear increase, while plasma albumin decreased, and platelets showed no apparent trend. The changes in blood cells and biochemical indices were most evident in relapsed patients and patients with COVID-19 within 2 weeks after chemotherapy. Latent class analysis showed that all severe COVID-19 patients were classified into class 1; the patients of class 1 showed a shorter interval between chemotherapy and COVID-19, and the higher baseline of AST, ALT, and LDH, the more cycles of chemotherapy and the advanced stage. CONCLUSIONS:The interval between chemotherapy and COVID-19 is associated with damage to tissues and organs. Clinical factors and laboratory factors indicate poor health conditions among patients with gynecological cancer and COVID-19.

BACKGROUND:High-risk human papillomavirus (HR-HPV) infection is the primary reason for cervical cancer and precancerous lesions in females. Specific immune alterations in pregnancy led to greater HR-HPV replication and reduced clearance of HR-HPV infection. This study retrospectively obtained and analyzed data from a tertiary hospital in Beijing, China. We aimed to ascertain both the genotype distribution and prevalence of HR-HPV in pregnant females. Moreover, we sought to analyze the association of HR-HPV with maternal-fetal pregnancy outcomes. METHODS:The retrospective observational cohort study was divided into two parts. Part I evaluated the genotype distribution and prevalence of HR-HPV. It encompassed 6285 pregnant women who underwent a routine pregnancy check-up, Thin Prep cytology test (TCT), and HR-HPV diagnosis during weeks 12-14 of gestation between January 1, 2013, and December 31, 2021. Part II analyzed the association between HR-HPV infection and maternal-fetal pregnancy outcome. Through a nearest-neighbor 1:1 propensity score matching (PSM), we matched HR-HPV-positive and HR-HPV-negative pregnant women using caliper width equal to 0.02. After PSM, 171 HR-HPV-positive and 171 HR-HPV-negative pregnant women were included to analyze the association between HR-HPV infection and maternal-fetal pregnancy outcome. RESULTS:In total 737 (11.73%) pregnant women were HR-HPV positive. The five most common genotypes of HR-HPV were HPV-52 (2.90%), HPV-58 (2%), HPV-16 (1.94%), HPV-51 (1.38%), and HPV-39 (1.29%). As for age-specific HPV prevalence, a "U-shaped" pattern was observed. The first and second peaks were detected in pregnant females aged <25 years and those aged ≥35 years, respectively. Our study found no significant difference between the HR-HPV-positive and the HR-HPV-negative pregnant females in the following maternal-fetal pregnancy outcomes: spontaneous abortion (1.2% for HR-HPV positive, 0% for HR-HPV negative, p = 0.478), preterm delivery (4.7% for HR-HPV positive, 5.3% for HR-HPV negative, p = 0.804), premature rupture of membrane (28.8% for HR-HPV positive, 22.8% for HR-HPV negative, p = 0.216), preeclampsia (7.6% for HR-HPV positive, 7.6% for HR-HPV negative, p = 1), oligohydramnios (8.2% for HR-HPV positive, 7% for HR-HPV negative, p = 0.683), fetal growth restriction (1.8% for HR-HPV positive, 0.6% for HPV negative, p = 0.615), placenta previa (1.2% for HR-HPV positive, 0.6% for HR-HPV negative, p = 1), postpartum hemorrhage (8.9% for HR-HPV positive, 11.2% for HR-HPV negative, p = 0.47). There was also no significant difference in delivery mode or birth weight between the two groups. CONCLUSIONS:HPV-16, 52, and 58 were the most prevalent infection genotypes in pregnant females. The study showed no significant differences between HR-HPV-positive and HR-HPV-negative groups in the maternal-fetal pregnancy outcomes.

Objective This study aimed to compare the clinical characteristics and surgical and histological outcomes of premenopausal and postmenopausal patients with adnexal torsion. Methods The electronic medical records of 278 patients with adnexal torsion proven by surgery were retrospectively reviewed from January 2012 to November 2023 in our hospital. The patients were divided into two groups (premenopausal and postmenopausal). Results The study included 226 (81.3%) premenopausal patients and 52 (18.7%) postmenopausal patients. The incidence of the most common symptoms (i.e., abdominal pain, nausea and/or vomiting) was not different between the two groups. However, the postmenopausal group had a longer interval from the onset of pain to admission, a larger size of adnexal mass, a longer operation time, more blood loss, and a longer hospital stay than the premenopausal group. Regarding the procedure, the premenopausal group underwent more conservative procedures than the postmenopausal group. The most common pathological findings in the two groups were benign tumors and tubal pathology The malignancy rate was similar in the two groups. Conclusions Premenopausal and postmenopausal women with adnexal torsion had similar main symptoms, such as abdominal pain and nausea and vomiting. However, the surgical and histological outcomes varied between these groups of women.

Background Precancerous lesions of cervical cancer exhibit characteristics indicative of natural progression. To prevent overtreatment of patients whose cervical intraepithelial neoplasia (CIN) in regression and to predict the onset of invasive cervical cancer at an early stage, we've identified the vaginal microbiome as a potential key factor, which is associated with both HPV infection and the various cervical intraepithelial neoplasia. This study aims to investigate the microbiome characteristics of patients with various cervical intraepithelial neoplasia. Methods Utilizing high-throughput 16S ribosomal RNA (16S rRNA) sequencing technology, a description of the characteristics and community composition of Vaginal Microbiota (VMB) was conducted among 692 Chinese women infected with the High-risk Human Papillomavirus (HR-HPV). Results As the grade of the lesions increased, the proportions of Lactobacillus and Pseudomonas demonstrated a significant declining trend, while the proportions of Gardnerella , Dialister , and Prevotella significantly increased. The diversity of the VMB was more significant in high-grade CIN. Furthermore, KEGG pathway enrichment analysis indicates that high-grade cervical intraepithelial neoplasia can inhibit various pathways, including those of phosphotransferase system, transcription factors, Fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism, which may contribute to the development of early cervical cancer symptoms. Conclusion Patients with CIN exhibit a distinct vaginal microbial profile characterized by a decrease in Lactobacillus and Pseudomonas , and an increase in Gardnerella , Prevotella , and Dialister . The proliferation and diminution of these two types of microbial communities are interrelated, suggesting a mutual restraint and balance among them. Disruption of this regulatory balance could potentially lead to the onset of cervical lesions and carcinogenesis. Retrospectively registered: This study was approved by the Ethics Committee of the Beijing Chaoyang Hospital affiliated with the Capital Medical University (NO.2023-S-415).

Background: Though sperm-associated antigen 5 (SPAG5) is highly expressed during the tumorigenesis and progression of various cancers, the impact of SPAG5 upon the most prevalent gynecologic cancer, endometrial cancer (EC), remains undefined. This study aims to investigate the impact of SPAG5 on EC cells.Methods: SPAG5 expression in EC tissues and its correlation with the overall survival of EC patients were inspected by bioinformatics. Exogenously upregulating or downregulating SPAG5 expression in EC cells was realized via transfection. Examination of EC cell viability, invasion, migration and apoptosis was accomplished by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl2-H-tetrazolium bromide (MTT), Transwell and scratch assays and flow cytometry. Western blot and quantitative real-time polymerase chain reaction were used to measure the expression levels of SPAG5 and mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) pathway-associated proteins and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-linked markers in EC cells. Results: High expression pattern of SPAG5 was observed in EC tissues (p < 0.05) and cells (p < 0.001), and was associated with a shorter survival time of EC patients. SPAG5 expression was successfully upregulated and downregulated via transfection with SPAG5 overexpression plasmid and shSPAG5, respectively (p < 0.01). Overexpression of SPAG5 increased the viability, migration, and invasion, reduced the apoptosis, and elevated the levels of phosphorylated (p)-AKT, p-PI3K, p-AKT/AKT and p-PI3K/PI3K. SPAG5 downregulation resulted in the opposite results (p < 0.05). However, changes in SPAG5 expression were not correlated with the level of p-ERK or ERK.Conclusion: Overexpression of SPAG5 drives in-vitro EC progression via activating the PI3K/AKT pathway.

Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8(+) T cells (P = 0.033), CD20(+) B cells (P = 0.023), CD56 NK cells (P = 0.041), PD-1(+) cells (P = 0.042), and PD-L1(+)CD68(+) macrophages (P = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20(+) cells (P = 0.046) and in the M1/M2 ratio (P = 0.038) as well as fewer tumors showing increase in the infiltration of CD56(bright) cells (P = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8(+) cells was positively associated with longer progression-free survival (PFS) (P = 0.011) and overall survival (OS) (P = 0.048). Post-NACT CD20(+) and CD163(+) macrophages (M2) infiltrates were associated with prolonged (P = 0.005) and shortened PFS (P = 0.021), respectively. Increase in the density of CD4(+) T cells was predictive for longer PFS (P = 0.022) and OS (P = 0.023). In the multivariate analysis, high density of CD8(+) cells pre-NACT (P = 0.042) were independently associated with improved OS.

BACKGROUND:Ureteral injury is common during gynaecological laparoscopic surgery. Real-time auto-segmentation can assist gynaecologists in identifying the ureter and reduce intraoperative injury risk. METHODS:A deep learning segmentation model was crafted for ureter recognition in surgical videos, utilising 3368 frames from 11 laparoscopic surgeries. Class activation maps enhanced the model's interpretability, showing its areas. The model's clinical relevance was validated through an End-User Turing test and verified by three gynaecological surgeons. RESULTS:The model registered a Dice score of 0.86, a Hausdorff 95 distance of 22.60, and processed images in 0.008 s on average. In complex surgeries, it pinpointed the ureter's position in real-time. Fifty five surgeons across eight institutions found the model's accuracy, specificity, and sensitivity comparable to human performance. Yet, artificial intelligence experience influenced some subjective ratings. CONCLUSIONS:The model offers precise real-time ureter segmentation in laparoscopic surgery and can be a significant tool for gynaecologists to mitigate ureteral injuries.

Purpose To build a machine learning model to predict histology (type I and type II), stage, and grade preoperatively for endometrial carcinoma to quickly give a diagnosis and assist in improving the accuracy of the diagnosis, which can help patients receive timely, appropriate, and effective treatment. Materials and Methods This study used a retrospective database of preoperative examinations (tumor markers, imaging, diagnostic curettage, etc.) in patients with endometrial carcinoma. Three algorithms (random forest, logistic regression, and deep neural network) were used to build models. The AUC and accuracy were calculated. Furthermore, the performance of machine learning models, doctors’ prediction, and doctors with the assistance of models were compared. Results A total of 329 patients were included in this study with 16 features (age, BMI, stage, grade, histology, etc.). A random forest algorithm had the highest AUC and Accuracy. For histology prediction, AUC and accuracy was 0.69 (95% CI=0.67-0.70) and 0.81 (95%CI=0.79-0.82). For stage they were 0.66 (95% CI=0.64-0.69) and 0.63 (95% CI=0.61-0.65) and for differentiation grade 0.64 (95% CI=0.63-0.65) and 0.43 (95% CI=0.41-0.44). The average accuracy of doctors for histology, stage, and grade was 0.86 (with AI) and 0.79 (without AI), 0.64 and 0.53, 0.5 and 0.45, respectively. The accuracy of doctors’ prediction with AI was higher than that of Random Forest alone and doctors’ prediction without AI. Conclusion A random forest model can predict histology, stage, and grade of endometrial cancer preoperatively and can help doctors in obtaining a better diagnosis and predictive results.

目的 探讨多种肿瘤细胞(human epididymis protein 4,HE4)表面的岩藻糖基化修饰.方法 分别应用免疫共沉淀、激光共聚焦法检测多种肿瘤细胞中HE4上Lewis y、Lewis x、Lewis a、Lewis b、sLewis a和sLewis x等6种岩藻糖基化抗原的修饰.结果 卵巢癌、肺癌等细胞中的HE4表面均发生了6种岩藻糖基化抗原的修饰,且乳糖系列Ⅱ型糖链的修饰明显高于Ⅰ型糖链.结论 多种肿瘤细胞HE4表面Ⅱ型糖链的修饰,尤其是Lewis y抗原修饰增加有利于肿瘤细胞的侵袭和播散.

FOXA1 is associated with malignant tumors, but the function of FOXA1 in EOC is unclear. HDAC3 can influence the proliferation, migration and invasion ability of EOC. In this study, we wanted to explore the function of FOXA1 in ovarian cancer and the relationship between HDAC3 and FOXA1.The expression of HDAC3 and FOXA1 was detected by immunohistochemical staining of primary lesions from 127 epithelial ovarian carcinoma patients. A proliferation assay, a Transwell assay, an apoptosis assay and animal experiments were used to assess the proliferation, invasion and apoptosis abilities of ovarian cancer cells before and after transfection with FOXA1. The relevance of the in vitro findings was confirmed in xenografts. The H-scores for FOXA1 and HDAC3 staining in FIGO stage III-IV were noticeably higher and predicted adverse clinical outcomes in patients with ovarian cancer. The expression level of HDAC3 was significantly correlated with the expression level of FOXA1. Invasion, proliferation and apoptosis capacity and tumor formation were decreased in the FOXA1-knockdown cells. Experiments in xenografts confirmed that HDAC3 mediated tumor formation. In conclusion, FOXA1 can be modulated by HDAC3 through the Wnt/β-catenin signaling pathway, and FOXA1 plays essential roles in the proliferation, apoptosis and invasion of EOC cell lines and xenograft experiments.

Circulating leukocytes are an important part of the immune system. The aim of this work is to explore the role of preoperative circulating leukocytes in serous ovarian carcinoma and investigate whether they can be used to predict survival prognosis. Routine blood test results and clinical information of patients with serous ovarian carcinoma were retrospectively collected. And to predict survival according to the blood routine test result the decision tree method was applied to build a machine learning model.The results showed that the number of preoperative white blood cells (p = 0.022), monocytes (p < 0.001), lymphocytes (p < 0.001), neutrophils (p < 0.001), and eosinophils (p < 0.001) and the monocyte to lymphocyte (MO/LY) ratio in the serous ovarian cancer group were significantly different from those in the control group. These factors also showed a correlation with other clinicopathological characteristics. The MO/LY was the root node of the decision tree, and the predictive AUC for survival was 0.69. The features involved in the decision tree were the MO/LY, differentiation status, CA125 level, neutrophils (NE,) ascites cytology, LY% and age.In conclusion, the number and percentage of preoperative leukocytes in patients with ovarian cancer is changed significantly compared to those in the normal control group, as well as the MO/LY. A decision tree was built to predict the survival of patients with serous ovarian cancer based on the CA125 level, white blood cell (WBC) count, presence of lymph node metastasis (LNM), MO count, the MO/LY ratio, differentiation status, stage, LY%, ascites cytology, and age.

Cervical cancer (CC) is the 4th principal source of cancer death in females with 604,000 new patients and 342,000 deaths in 2020 worldwide. It has been extensively shown that circRNAs are involved in regulating CC development. Nevertheless, the function and mechanisms of hsa_circ_0004543 in regulating CC need to be clearly elucidated. Herein, hsa_circ_0004543 expressions were compared between 40 paired paracancerous and cancerous specimens from CC patients and between 6 CC cell lines and a normal human cervical epithelial cell line based on qRT-PCR. Potential complementary binding sites between hsa-miR-217 and hsa_circ_0004543 were predicted using the interactome, while binding sites for the hypoxia-inducible factor-1a (HIF-1a) were predicted by TargetScan. The function and mechanism of hsa_circ_0004543 in the development of CC were estimated by silencing hsa_circ_0004543 with/without hsa-miR-217 or HIF-1a overexpression. The association between gene expressions was evaluated with Pearson's correlation analysis. Molecular mechanisms were explored by ribonucleic acid (RNA) pulldown, dual-luciferase activity, and rescue experimental assays. Our results revealed that the hsa_circ_0004543 expression was considerably increased in CC tissues and cells. Its silencing repressed proliferation and metastasis, while it increased apoptosis of CC cells. The investigation of the mechanism showed that hsa-miR-217 silencing or HIF-1a overexpression rescued hsa_circ_0004543, and silencing inhibited malignant phenotypes of CC cells. hsa_circ_0004543 upregulated the HIF-1α expression by sponging hsa-miR-217 in CC development. Therefore, the hsa_circ_0004543 functioned as a competing endogenous RNA (ceRNA) of hsa-miR-217 to increase CC oncogenesis and metastasis by the upregulation of the HIF-1α expression. Consequently, targeting the hsa_circ_0004543/hsa-miR-217/HIF-1α axis might be a potential treatment approach for CC.

e17605 Background: Platinum-based neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) and adjuvant chemotherapy has been an established alternative for advanced epithelial ovarian cancer (EOC). The chemotherapy response score (CRS) has been applied to assess the efficacy of NACT in high-grade serous ovarian cancer (HGSOC). The purpose of this study was to assess the effect of NACT on tumor immune microenvironment (TIME) of HGSOC, and the correlation between the TIME and CRS. Methods: All patients underwent NACT with IDS. Formalin-fixed paraffin-embedded tissue samples were collected from pretreatment biopsy specimens and the corresponding post-NACT surgical specimens. The densities and percentage of various cell populations within the TIME were analyzed by multiplex immunohistochemistry (3DMedcines Inc.), including specific tumor infiltrating lymphocytes (TILs) (CD8+T cell, FOXP3+CD4+Treg cell and CD20+B cell), tumor associated macrophages (TAMs), NK cells (CD56 dim and CD56 bright). Patients were divided into three groups according to CRS based on pathological reaction of surgical specimens: CRS1 shows no or minimal response, CRS2 shows moderate response and CRS3 usually shows complete or near-complete response. Statistical analyses were performed using GraphPad Prism 7.0. P < 0.05 was considered statistically significant. Results: A total of 25 HGSOC patients were enrolled in this study, 32% (8/25) of patients with CRS 1, 64% (16/25) with CRS 2, and 4% (1/25) with CRS 3. After NACT, patients with CRS 2 or 3 had a significant increase of the densities of CD20+B cells in stroma (pre-NACT 15.71/mm3 vs. post-NACT 87.82/mm3, p = 0.048). We also observed borderline significant increases of percentage of CD20+B cells, the densities and percentage of CD8+T cells in stroma after NACT (pre-NACT vs. post-NACT, 0.32% vs.1.54%, 56.35/mm3 vs. 311.35/mm3, 0.95% vs. 5.48%, respectively). Meanwhile, no significant change in CD4+T, TAMs and NK cells. In patients with CRS 1, we observed a significant increase of the densities and percentage of CD4+FOXP3+Treg in stroma (pre-NACT vs. post-NACT, 1.38/mm3 vs. 19.75/mm3, p = 0.01; 0.04% vs. 0.41%, p = 0.017, respectively), while CD8+T, CD20+B, TAMs and NK cells did not change significantly. Additionally, we found a significant difference in CD56 bright NK infiltration when comparing CRS 2 or 3 group with CRS1 group in post-NACT (0.5/mm3 vs.12/mm3, p = 0.049; 0.005% vs. 0.23%, p = 0.048). Conclusions: These data suggest immune infiltrate in TIME may serve as a biomarker to predict response to NACT in HGSOC. The infiltration of CD8+ T and CD20+ B cell was more pronounced in CRS2 or 3, while the enhanced infiltration of FOXP3+CD4+Treg cells is associated with immunosuppressive TIME and poor response (CRS1). The mechanism of lymphocyte regulation is not completely understood, thereby deserving further investigation.