PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

Pelvic floor muscle strength and influencing factors based on vaginal manometry among healthy women at different life stages: A multicentre cross-sectional study.

OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.

The molecular mechanism of ferroptosis-induced spontaneous abortion based on bioinformatics approach.

Spontaneous abortion (SA) is a prevalent placental dysfunction, and ferroptosis may play a crucial role in placental dysfunction and the development of SA. In this study, we employed data mining and analysis techniques to investigate the biological mechanism of SA induced by ferroptosis, resulting in the identification of a total of 79 ferroptosis-related genes in SA were identified. Among them, 3 co-expression modules of ferroptosis risk genes, ten significant functions and six biologically significant pathways were obtained 61 pairs of differentially expressed miRNA-ferroptosis factor relationships were identified, and WIPI1 and GSN were expressed at significantly higher levels in SA. This is extremely helpful for future research on SA.

MiR-4319 targets tuftelin 1 to reduce malignancy of cervical cancer cells.

Cervical cancer (CC) is the most common malignant tumor of female reproductive system. MiR-4319 has been identified as an anti-oncogene in various cancers. In the present study, role of miR-4319 in CC was identified. Colony formation, flow cytometer, wound healing, and transwell assays were used to detect CC cell proliferation, apoptosis, migration, and invasion. The expression of miR-4319 was decreased in clinical CC tissues and CC cell lines. Upregulation of miR-4319 suppressed cell viability, proliferation, migration, and invasion, and induced cell apoptosis in CC cells. Moreover, tuftelin 1 (TUFT1) was verified as a direct target of miR-4319, as confirmed by dual-luciferase reporter assay. Additionally, TUFT1 expression was remarkably increased in clinical CC tissues and CC cell lines and was negatively associated with miR-4319 expression. Furthermore, overexpression of TUFT1 partially restored the effects of miR-4319 mimic on cell viability, proliferation, migration, invasion, and cell apoptosis in CC cells. To conclude, miR-4319 played an anti-cancer role in the occurrence and development of CC, which might be achieved by targeting TUFT1.

FBXO22 inhibits proliferation and metastasis of cervical cancer cells by mediating ubiquitination-dependent degradation of GAK.

Cervical cancer is one of the recognized malignant tumors of female reproductive system. At present, the research and development of biomarkers has attracted increasing attention, and the wide application of clinical cervical cancer screening strategies has significantly reduced its morbidity and mortality. A member of the F-box protein family, FBXO22, is involved in cell cycle, DNA damage repair and many other processes. Dysregulation of FBXO22 plays an important role in the occurrence and development of various tumors, including ovarian cancer, liver cancer and lung cancer. Nevertheless, the effect of FBXO22 in cervical cancer needs further investigation. We found that FBXO22 inhibited cervical cancer cell proliferation, migration and invasion. The results of proteomics studies suggested FBXO22 appears to target the Cyclin G Associated Kinase (GAK) for degradation. The combined results of analysis of cultured cells with altered abundance of FBXO22 by depletion or over-expression in the presence or absence of proteasomal inhibitor, comparison of protein decay rate, as well as cellular ubiquitination, support a hypothesis that FBXO22 mediates the ubiquitin-dependent degradation of GAK. Taken together, our data suggest that FBXO22 has a protective role in cervical cancer.

Development of gene panel for predicting recurrence in early-stage cervical cancer patients.

Cervical cancer (CC) is a common malignancy affecting women worldwide. Our objective was to develop a consensus-based gene panel using multi-omics data that could effectively predict recurrence in early-stage cervical cancer patients. We utilized the "Multi-Omics Consensus Integration Analysis (MOVICS)" package for consensus clustering design to integrate multiple omics datasets and improve the molecular classification landscape of early-stage CC. We identified the "resting and naive" tumor microenvironment (TME) as cancer subtype (CS) 2. Leveraging the feature genes from the CS classifier, we employed machine learning algorithms to identify a gene panel, including ALDH1A1, CLDN10, MUC13, and C10orf99, which could generate a consensus machine learning-driven score (CMLS) for each patient. Stratifying patients into high and low CMLS groups resulted in Kaplan-Meier curves demonstrating a significant difference in recurrence rates between the two groups. This difference remained significant even after adjusting for clinical features in multivariate Cox regression analysis, with the risk ratio of CMLS surpassing that of clinical characteristics. Furthermore, the TME exhibited notable differences between the different CMLS groups, suggesting that patients with low CMLS may exhibit a better response to immunotherapy. This study highlights the potential of the CMLS approach in predicting recurrence in early-stage cervical cancer patients and provides a screening model for selecting patients suitable for immunotherapy.

LINC00460 promotes angiogenesis by enhancing NF-κB-mediated VEGFA expression in cervical cancer cells.

Angiogenesis is a characteristic of tumor development and is key for tumor growth and metastasis. LINC00460 is a long non-coding RNA that plays important yet complex roles in cancer development and progression. Here, we explored the functional mechanism of action of LINC00460 in cervical cancer (CC) angiogenesis for the first time. We found that conditioned medium (CM) from LINC00460-knockdown CC cells attenuated human umbilical vein endothelial cell (HUVEC) migration, invasion, and tube formation, whereas LINC00460 upregulation had the opposite effects. Mechanistically, LINC00460 stimulated VEGFA transcription. Suppressing VEGF-A reversed the effects of CM from LINC00460-overexpressing CC cells on HUVEC angiogenesis. Recombinant VEGFA eliminated the suppressive effects of CM from LINC00460-knockdown CC cells. Furthermore, LINC00460 enhanced VEGFA expression and promoted angiogenesis by activating the NF-κB pathway. Our data illustrate that LINC00460 can promote angiogenesis by activating the NF-κB-VEGFA axis, suggesting that the axis is a promising target for blocking tumor angiogenesis.

LncRNA HOTAIR Promotes Chemoresistance by Facilitating Epithelial to Mesenchymal Transition through miR-29b/PTEN/PI3K Signaling in Cervical Cancer.

Long non-coding RNA HOTAIR has been revealed to participate in the tumorigenesis of various cancers. However, the mechanism of HOTAIR involvement in cervical cancer has not been identified. Hence, this study aimed to explore the oncogenic and chemoresistant roles of HOTAIR in cervical cancer, and its underlying mechanism. RT-PCR, Western blot, and Luciferase assay were employed to determine the relationship of HOTAIR with miR-29b and PTEN and to study the role of HOTAIR in cervical cancer. CCK8 assay, cell migration, and invasion assay were used to reveal the role of HOTAIR in cervical cancer cell proliferation and metastasis. The inhibitory dose of chemotherapeutics was determined by CCK8 assay using probit analysis. HOTAIR was found to bind with miR-29b, and a negative correlation existed between HOTAIR and miR-29b expression in cervical cancer cells. In addition, HOTAIR promoted the migration and proliferation of cervical cancer cell lines HeLa and Siha, showing effects opposite to miR-29b. Further, HOTAIR facilitated the resistance of both HeLa and Siha cells against cisplatin, paclitaxel and docetaxel, whereas miR-29 suppressed the resistance of both cervical cancer cells against the 3chemotherapeutics. In addition, HOTAIR enhanced epithelial-to-mesenchymal transition (EMT), while miR-29b exerted an inhibitory effect on EMT. In cervical cancer cells, miR-29b did not affect promoter methylation of PTEN but regulated PTEN expression by targeting SP1. Transfection of miR-29b mimics led to a significant downregulation of PI3K. HOTAIR promotes chemoresistance by facilitating EMT through the miR-29b/PTEN/PI3K axis in cervical cancer.

Deep Neural Networks Offer Morphologic Classification and Diagnosis of Bacterial Vaginosis.

Bacterial vaginosis (BV) is caused by the excessive and imbalanced growth of bacteria in vagina, affecting 30 to 50% of women. Gram staining followed by Nugent scoring based on bacterial morphotypes under the microscope is considered the gold standard for BV diagnosis; this method is often labor-intensive and time-consuming, and results vary from person to person. We developed and optimized a convolutional neural network (CNN) model and evaluated its ability to automatically identify and classify three categories of Nugent scores from microscope images. The CNN model was first established with a panel of microscopic images with Nugent scores determined by experts. The model was trained by minimizing the cross-entropy loss function and optimized by using a momentum optimizer. The separate test sets of images collected from three hospitals were evaluated by the CNN model. The CNN model consisted of 25 convolutional layers, 2 pooling layers, and a fully connected layer. The model obtained 82.4% sensitivity and 96.6% specificity with the 5,815 validation images when altered vaginal flora and BV were considered the positive samples, which was better than the rates achieved by top-level technologists and obstetricians in China. The capability of our model for generalization was so strong that it exhibited 75.1% accuracy in three categories of Nugent scores on the independent test set of 1,082 images, which was 6.6% higher than the average of three technologists, who are hold bachelor's degrees in medicine and are qualified to make diagnostic decisions. When three technologists ran one specimen in triplicate, the precision of three categories of Nugent scores was 54.0%. One hundred three samples diagnosed by two technologists on different days showed a repeatability of 90.3%. The CNN model outperformed human health care practitioners in terms of accuracy and stability for three categories of Nugent score diagnosis. The deep learning model may offer translational applications in automating diagnosis of bacterial vaginosis with proper supporting hardware.

MicroRNA-301a Promotes Cell Proliferation and Resistance to Apoptosis through PTEN/PI3K/Akt Signaling Pathway in Human Ovarian Cancer.

BACKGROUND: MicroRNAs are endogenous small noncoding RNAs, which play a critical role in regulating various biological and pathologic processes. Furthermore, miR-301a has been detected to be overly expressed in tumorigenic progression of ovarian cancer. However, the effects of miR-301a on ovarian cancer are still unclear. OBJECTIVE: The objective of this study is to investigate the molecular mechanisms of miR-301a in epithelial ovarian cancer cells. METHODS: The miR-301a expression in ovarian cancer cells was detected. Then, cell proliferation, cell cycle, and apoptosis of the miR-301a-mimic-transfected ovarian cancer cells were determined, as well as the effects of the miR-301a mimic on the PTEN/phosphoinositide 3-kinase (PI3K) signaling pathway were explored. RESULTS: We found that the miR-301a expression levels were markedly upregulated in ovarian cancer tissues and cells, and upregulation of miR-301a-promoted cell viability and proliferation. Our results also showed that the miR-301a-mimic accelerated cell cycle progression of ovarian cancer cells by targeting the CDK4/Cyclin-D1 pathway but not the CDK2/Cyclin-E pathway. Moreover, transfection of the miR-301a mimic into ovarian cancer cells could decrease the PTEN expression while increasing the PI3K and Akt phosphorylation, as compared with the miR-301a inhibitor group and the negative control group. CONCLUSION: Therefore, miR-301a should be an oncogene in ovarian cancer, and overexpression of miR-301a promoted proliferation of ovarian cancer cells by modulating the PTEN/PI3K/Akt signaling pathway.

A newly identified lncRNA H1FX-AS1 targets DACT1 to inhibit cervical cancer via sponging miR-324-3p.

BACKGROUND: Cervical cancer (CC) is the 4th most common cancer-related death in gynecological cancer worldwide. It has been reported that many lncRNAs contribute to oncogenesis although the fundamental mechanisms are basically unknown. Here, we aimed to identify a novel lncRNA H1FX-AS1 and explore a ceRNA network in CC oncogenesis and progression. METHODS: The expression level and the association with the prognosis of H1FX-AS1 in CC patients were analyzed based on Cancer Genome Atlas (TCGA) datasets, and further verified in 50 CC patients. The biological role of H1FX-AS1 was investigated in vitro and in vivo by over-expression of H1FX-AS1 in CC cells; the potential binding sites between H1FX-AS1 and miRNA, between miR-324-3p and DACT1 were predicted by LncBASE and Targetscan respectively, which were further verified by dual-luciferase reporter assay, RNA pull-down and point mutation; the relationship between genes was analyzed by Pearson correlation; the rescue experiments were used to further explore the involved molecular mechanism. RESULTS: Lower H1FX-AS1 expression in CC tissues was found to be associated with the poor prognosis of CC patients. Over-expression of H1FX-AS1 inhibited CC cell proliferation, migration and invasion, while induced apoptosis by sponging miR-324-3p to up-regulate the DACT1 expression level. CONCLUSION: A novel lncRNA H1FX-AS1 was identified, which acted as a competing endogenous RNA (ceRNA) of miR-324-3p to inhibit DACT1 mediated CC progression. Therefore, H1FX-AS1 is a new prognostic predictor and targeting the factors in the H1FX-AS1/miR-324-3p/DACT1 axis is the novel potential therapeutic strategy for CC.

Effect of endometrial injury during menstruation on clinical outcomes in frozen-thawed embryo transfer cycles: A randomized control trial.

AIM: To explore the clinical effect of endometrial injury (EI) on the third day of the menstrual cycle before frozen-thawed embryo transfer (frozen-thawed ET) on patients experienced two or more implantation failures. METHODS: A total of 200 patients who suffered at least two failed hormone-replacement therapies and frozen-thawed ET were randomly divided into two groups: EI group and control group (n = 100 in each group). Patients in the EI group received local EI with a Pipelle catheter on the third day of the menstrual cycle before frozen-thawed ET. Primary outcomes were live birth, clinical pregnancy and implantation rates. Secondary outcomes were biochemical, multiple and ectopic pregnancy rates and abortion rates. RESULTS: The rate of live birth in EI group (51.00%) was significantly higher than that of control group (36.00%) (P = 0.032). Clinical pregnancy and implantation rates in EI group were significantly higher comparing to control group (64.00% vs 48.00%, P = 0.023 and 46.74% vs 30.11%, P = 0.001). The rate of multiple pregnancy in EI group (37.50%) was significantly higher than that of control group (18.75%) (P = 0.031). No significant difference in ectopic pregnancy rate and abortion rate was observed between EI group and control group. CONCLUSION: Applying EI to patients experienced two or more implantation failures on the third day of the menstrual cycle before frozen-thawed ET can improve clinical outcomes.

LncRNA CASC11 promotes the cervical cancer progression by activating Wnt/beta-catenin signaling pathway.

BACKGROUND: Studies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression. MATERIALS: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/ß-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation. RESULTS: We discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients' survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell's proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/ß-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo. CONCLUSION: Our study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/ß-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.

Effect of vasopressin injection technique in laparoscopic excision of bilateral ovarian endometriomas on ovarian reserve: prospective randomized study.

STUDY OBJECTIVE: To evaluate the effects of vasopressin injection technique in laparoscopic cystectomy on ovarian reserve in patients with bilateral endometriomas. DESIGN: Randomized prospective study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Eighty-six women with bilateral endometriomas. INTERVENTIONS: Laparoscopic cystectomy of bilateral endometriomas was performed using different techniques including laparoscopic cystectomy by stripping without injection (control group), laparoscopic cystectomy by stripping with injection of saline solution (saline group), and laparoscopic cystectomy by stripping with vasopressin injection technique (VIT group). MEASUREMENTS AND MAIN RESULTS: The number of coagulation events on the ovarian cortex for hemostasis was counted in different groups, and the thickness of ovarian tissues removed was measured. The basal follicle-stimulating hormone (FSH) level was determined before surgery and at 3-, 6-, and 12-month follow-up after laparoscopic cystectomy in the different groups. In the saline group, fewer coagulation events were required to achieve hemostasis, less ovarian tissues were removed, and lower preoperative FSH levels were detected than in the control group (p < .01). In the VIT group, even fewer coagulation events (p < .01) and lower preoperative FSH levels (p < .01) were detected than in the saline group. There was no significant difference in the thickness of ovarian tissues removed in the 2 groups (p > .05). Basal FSH levels were significantly different before and after surgery in the control and saline groups (p < .01) but not in the VIT group (p > .05). CONCLUSION: Vasopressin injection is an ideal procedure to reduce damage from usual laparoscopic cystectomy of bilateral ovarian endometriomas to protect ovarian reserve.

Expression of Sox2 in cervical squamous cell carcinoma.

PURPOSE: Sox2, one of the genes that maintains self-renewal of embryonic stem cells and relates to the differentiation potential of these cells, is abnormaly expressed in various human tumors. We investigated the expression Sox2 in normal cervix and cervical squamous cell carcinoma (SCC), and we also assessed the prognostic significance of Sox2 expression in FIGO stage I-II cervical SCC. METHODS: Immunohistochemistry was performed to define the expression of Sox2 in 20 normal cervical tissue samples and 55 samples of cervical SCC. Correlations with clinicopathological characteristics were determined by chi-square test. The prognostic impact of Sox2 expression with regard to overall disease-free survival (DFS) was determined by the Kaplan-Meier method. RESULTS: The positive expression rate in cervical SCC was 74.5% (41/55), while in normal cervix it was 20.0% (4/20; p=0.000. In addition, the expression of Sox2 did not correlate with clinical factors (p>0.05). The overall DFS rates with negative and positive expressions of Sox2 were 35.7 and 29.3%, respectively (p=0.360). CONCLUSIONS: Our results show that Sox2 was overexpressed in FIGO stage I-II cervical SCC, indicating that overexpressed Sox2 may play an important role in the carcinogenesis of cervical SCC. Besides, we found that the expression of Sox2 had no relation to clinical factors and prognosis.

TET3-mediated DNA demethylation modification activates SHP2 expression to promote endometrial cancer progression through the EGFR/ERK pathway.

OBJECTIVE: Src homology phosphotyrosin phosphatase 2 (SHP2) has been implicated in the progression of several cancer types. However, its function in endometrial cancer (EC) remains unclear. Here, we report that the ten-eleven translocation 3 (TET3)-mediated DNA demethylation modification is responsible for the oncogenic role of SHP2 in EC and explore the detailed mechanism. METHODS: The transcriptomic differences between EC tissues and control tissues were analyzed using bioinformatics tools, followed by protein-protein interaction network establishment. EC cells were treated with shRNA targeting SHP2 alone or in combination with isoprocurcumenol, an epidermal growth factor receptor (EGFR) signaling activator. The cell biological behavior was examined using cell counting kit-8, colony formation, flow cytometry, scratch assay, and transwell assays, and the median inhibition concentration values to medroxyprogesterone acetate/gefitinib were calculated. The binding of TET3 to the SHP2 promoter was verified. EC cells with TET3 knockdown and combined with SHP2 overexpression were selected to construct tumor xenografts in mice. RESULTS: TET3 and SHP2 were overexpressed in EC cells. TET3 bound to the SHP2 promoter, thereby increasing the DNA hydroxymethylation modification and activating SHP2 to induce the EGFR/extracellular signal-regulated kinase (ERK) pathway. Knockdown of TET3 or SHP2 inhibited EC cell malignant aggressiveness and impaired the EGFR/ERK pathway. Silencing of TET3 inhibited the tumorigenic capacity of EC cells, and ectopic expression of SHP2 or isoprocurcumenol reversed the inhibitory effect of TET3 knockdown on the biological activity of EC cells. CONCLUSION: TET3 promoted the DNA demethylation modification in the SHP2 promoter and activated SHP2, thus activating the EGFR/ERK pathway and leading to EC progression.

ULK2 suppresses ovarian cancer cell migration and invasion by elevating IGFBP3.

Background: Ovarian cancer is an aggressive malignancy with high mortality known for its considerable metastatic potential. This study aimed to explore the expression and functional role of Unc-51 like autophagy activating kinase 2 (ULK2) in the progression of ovarian cancer. Methods: ULK2 expression patterns in ovarian cancer tissues as well as benign tumor control samples obtained from our institution were evaluated using immunohistochemistry. Cell counting kit 8 and Transwell assays were applied to assess the effects of ULK2 overexpression on cell proliferation, migration and invasion, respectively. RNA sequencing was performed to explore potential mechanisms of action of ULK2 beyond its classical autophagy modulation. Results: Our experiments showed significant downregulation of ULK2 in ovarian cancer tissues. Importantly, low expression of ULK2 was markedly correlated with decreased overall survival. In vitro functional studies further demonstrated that overexpression of ULK2 significantly suppressed tumor cell proliferation, migration, and invasion. RNA sequencing analysis revealed a potential regulatory role of ULK2 in the insulin signaling pathway through upregulation of insulin-like growth factor binding protein-3 (IGFBP3) in ovarian cancer cells. Conclusions: In summary, the collective data indicated that ULK2 acted as a tumor suppressor in ovarian cancer by upregulating the expression of IGFBP3. Our study underscores the potential utility of ULK2 as a valuable prognostic marker for ovarian cancer.

Retroperitoneal dermoid cyst complicated with uterine adenomyoma: a case report and literature review.

Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a patient with a pelvic mass diagnosed as a retroperitoneal dermoid cyst at our hospital. We analyzed this case and conducted a literature review, to mitigate the risk of misdiagnosis and enhance the treatment of retroperitoneal masses.

ERBB3 mediates the PI3K/AKT/mTOR pathway to alter the epithelial­mesenchymal transition in cervical cancer and predict immunity filtration outcome.

Cervical cancer is the fourth most common cancer among women worldwide, and the prognosis of advanced/recurrent cervical cancer remains poor. Metastasis and invasion of this type of cancer are closely associated with the tumor microenvironment. Studying the complex interactions between tumor progression and immune cells or stromal cells can provide new insights into treatment for patients with aggressive tumor, recurrence and drug resistance. In the present study, a bioinformatics method (Gene Expression Profiling Interactive Analysis, differentially expressed genes, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interactions and survival analysis) was used to explore the mRNA and protein level discrepancy gene signature of ERBB3 via the PI3K/AKT/mTOR pathway from the speculation in immuno-oncology and experimental verification of different cervical cancer cell lines. The high expression of ERBB3 in cervical cancer tissues (especially HPV-positive and adenocarcinoma-related) promoted the activation of the PI3K/AKT/mTOR pathway. The increased expression of MMP9 changed the macrophage infiltration in the tumor microenvironment and affected prognosis of patients with cervical cancer. In conclusion, the present study identified 14 EMT-related genes and 30 genes involved in the PI3K/AKT/mTOR pathway in cervical cancer, and they might provide novel clues for future treatment. The MMP family may be a notable factor associated with tumor cells and immune cells.

Profiling of immune responses by lactate modulation in cervical cancer reveals key features driving clinical outcome.

Cervical cancer is still an important problem perplexing health management in developing countries. Previous studies have shown that cervical cancer cells show markers of aerobic glycolysis, suggesting that these tumors may secrete lactic acid. Through the biological characterization of lactate gene in tumor and its relationship with immune cells in tumor microenvironment, a lactate scoring system capable of evaluating cancer prognosis was constructed to explore the molecular mechanism of lactate metabolism disorder affecting prognosis. 29 hub genes in this study were differentially expressed in cervical cancer, including 24 genes related to lactate metabolism, LDHA in Lactate dehydrogenase (LDH) group, SLC16A3 in Monocarboxylate transporters (MCT) group and three Histone lactation modification related genes (EP300, ACAT1, ACACA). More importantly, we found that from an epigenetic point of view, histone lactation plays an important role in the pathogenesis and prognosis of cervical cancer. Mainly affect the prognosis of the disease through changes in the infiltration of plasmacytoid Dendritic Cell (pDC) and Central Memory T cell (Tcm) in the tumor immune microenvironment. Lactate inhibition may be a useful tool for anticancer therapy.