Advances of Artificial Intelligence Application in Medical Imaging of Ovarian Cancers

Ovarian cancer is one of the three most common gynecological cancers in the world,and is regarded as a priority in terms of women’s cancer.In the past few years,many researchers have attempted to develop and apply artificial intelligence(AI)techniques to multiple clinical scenarios of ovarian cancer,especially in the field of medical imaging.AI-assisted imaging studies have involved computer tomography(CT),ultrasonography(US),and magnetic resonance imaging(MRI).In this review,we perform a literature search on the published studies that using AI techniques in the medical care of ovarian cancer,and bring up the advances in terms of four clinical aspects,including medical diagnosis,pathological classification,targeted biopsy guidance,and prognosis prediction.Meanwhile,current status and existing issues of the researches on AI application in ovarian cancer are discussed.

hGBP-1 Expression Predicts Shorter Progression-Free Survival in Ovarian Cancers, While Contributing to Paclitaxel Resistance

Ovarian cancer is the gynecological cancer with the poorest prognosis. One significant reason is the development of resistance to the chemotherapeutic drugs used in its treatment. The large GTPase, hGBP-1, has been implicated in paclitaxel resistance in ovarian cell lines. Forced expression of hGBP-1 in SKOV3 ovarian cancer cells protects them from paclitaxel-induced cell death. However, prior to this study, nothing was known about whether hGBP-1 was expressed in ovarian tumors and whether its expression correlated with paclitaxel resistance. hGBP-1 is expressed in 17% of ovarian tumors from patients that have not yet received treatment. However, at least 80% of the ovarian tumors that recurred after therapies that included a taxane, either paclitaxel or docetaxel, were positive for hGBP-1. In addition, hGBP-1 expression predicts a significantly shorter progression-free survival in ovarian cancers. Based on these studies, hGBP-1 could prove to be a potential biomarker for paclitaxel resistance in ovarian cancer.

Immune pathway through endometriosis to ovarian cancer

Endometriosis is an estrogen-dependent inflammatory disease,defined by the presence of functional endometrial tissue outside of the uterine cavity.This disease is one of the main gynecological diseases,affecting around 10%-15%women and girls of reproductive age,being a common gynecologic disorder.Although endometriosis is a benign disease,it shares several characteristics with invasive cancer.Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer,representing an earlier stage of neoplastic processes.This is particularly true for women with clear cell carcinoma,low-grade serous carcinoma and endometrioid.However,the carcinogenic pathways between both pathologies remain poorly understood.Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers(EAOCs)via pathways associated with oxidative stress,inflammation,and hyperestrogenism.This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis,specifically focusing on the complex relationship between the immune response to endometriosis and cancer,including the molecular mechanisms and their ramifications.Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

Efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer

BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditional open surgery is the main treatment for ovarian cancer,but it has the disadvantages of big trauma and slow recovery.With the continuous development of minimally invasive technology,minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery.However,the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.AIM To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.METHODS The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively.According to the different surgical treatment methods,patients were divided into study group and control group(45 cases in each group).The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer,while the control group received traditional open surgery for ovarian cancer.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),clinical efficacy and safety of the two groups were compared.RESULTS The intraoperative blood loss,length of hospital stay,postoperative gas evacuation time,and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group(P<0.05).The incidence of postoperative complications in the study group was significantly lower than in the control group(P<0.05).The two groups had no significant differences in the preoperative adrenocorticotropic hormone(ACTH),androstenedione(AD),cortisol(Cor),cluster of differentiation 3 positive(CD3+),and cluster of differentiation 4 positive(CD4+)indexes(P>0.05).In contrast,postoperatively,the study group's ACTH,AD,and Cor indexes were lower,and the CD3+and CD4+indexes were higher than those in the control group(P<0.05).CONCLUSION Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety,improve the short-term prognosis and quality of life of patients,and is worth popularizing.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

LncRNA IDH1-AS1 sponges miR-518c-5p to suppress proliferation of epithelial ovarian cancer cell by targeting RMB47

Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is unknown.Therefore,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft assays.We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western blotting.We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells.High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC.IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation.The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression.Furthermore,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown.Taken together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.

Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor survival.it has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and development.However,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still unclear.Methods:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian carcinoma.Cytotoxicity assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer cells.RNA pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer cells.Results:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian cancer.Functional experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this function.Mechanistically,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

Primary ovarian cancer combined with primary fallopian tube cancer:A case report

BACKGROUND Low grade serous carcinoma of the ovary(LGSOC)is a rare type of epithelial ovarian cancer with a low incidence rate.The origin of ovarian cancer has always been a hot topic in gynecological oncology research,and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes.Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system.There are only a few reports in the literature,but the mortality rate is very high.But in clinical practice,fallopian tube cancer is very common,but in most cases,it is classified as ovarian cancer.CASE SUMMARY We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment.The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube.No special treatment was performed after the surgery,and the patient was instructed to undergo regular follow-up without any signs of disease progression.CONCLUSION The prognosis of LGSOC is relatively good,over 80%of patients still experience disease recurrence.

Long-term complete response to anti-programmed-death-1 monotherapy in a patient with relapsed and refractory ovarian adenocarcinoma: A case report

BACKGROUND Ovarian cancer is the most common malignant tumor of the female reproductive system,and the survival rate of patients with relapsed and refractory ovarian cancer is very low.CASE SUMMARY Here,we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy.Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful;however,her tumor relapsed.Subsequent second-line chemotherapy,targeted agents,and other treatments were ineffective,as the tumor continued to recur and metastasize.Anti-programmed cell death-1(PD-1)monotherapy(tislelizumab)completely alleviated the tumor,and the multiple metastatic tumors disappeared.To date,the patient has used anti-PD-1 for 32 months,experiencing no disease progression and maintaining good health without additional treatment.CONCLUSION This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors.Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.

Exploring the molecular mechanisms and potential therapeutic strategies of ferroptosis in ovarian cancer

The morbidity rate of ovarian cancer,a malignant tumour in gynaecological tumours,is rising,and it is considered to be the most lethal cancer.The majority of patients are typically diagnosed during the advanced stages of the illness due to the elusive characteristics of ovarian cancer and an absence of highly sensitive and specific diagnostic indicators.Surgical excision of the lesions,along with chemotherapy,is the conventional treatment for ovarian cancer;however,resistance to platinum-based chemotherapeutic drugs and molecular targeted therapies frequently arises.Improving the survival rate and prognosis of patients with end-stage or recurring ovarian cancer requires the identification of new therapeutic targets due to the absence of efficient medications,and this has emerged as a highly demanding issue.Studies have demonstrated that ferroptosis effectively hinders the proliferation of ovarian cancer and induces the demise of malignant cells.Ferroptosis is composed of the cystine/glutamate antiporter system(the system Xc-)and glutathione peroxidase 4(GPX4).Solute carrier family 7 member 11(SLC7A11)and solute carrier family 3 member 2(SLC3A2)play crucial roles in the regulation of ferroptosis by facilitating the uptake of cystine into cells and the efflux of glutamate out of cells,respectively.In cells,GPX4 is the exclusive enzyme employed for reducing liposomal peroxide through glutathione peroxidase activity.The occurrence of ferroptosis in ovarian cancer is strongly associated with three main pathways,namely,the GPX4-glutathione(GSH)protective pathway,the ferroptosis suppressor protein 1(FSP1)-coenzyme Q10(CoQ10)protective pathway,and the guanosine 5'-triphosphate cyclohydrolase I(GCH1)protective pathway.In ovarian cancer cells,the postsynaptic density-95,discs-large,zona occludens 1(PDZ)-binding motif-angiopoietin-like 4-nicotinamide adenine dinucleotide phosphate oxidases 2(TAZ-ANGPTL4-NOX2)pathway can be regulated by Yes-associated protein(YAP)/TAZ,a downstream component of the Hippo pathway,leading to the modulation of ferroptosis.By targeting microRNA-587,lncRNA ADAMTS9 antisense RNA 1(ADAMTS9-AS1)can modulate the expression of SLC7A11 and reduce the occurrence of ferroptosis.Although ferroptosis holds promise in overcoming the resistance mechanism,there remain obstacles in utilizing it as a cancer treatment,including the potential harm of drugs to healthy cells.Hence,additional investigations are required to formulate safer and more efficient chemotherapy protocols for the treatment of ovarian cancer and other malignancies.

Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment responses.AIM To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural networks.METHODS Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus.Mitochondrial genes were sourced from the MitoCarta3.0 database.The discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation cohort.Using the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were predicted.RESULTS In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy model.The average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation cohort.The average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation cohort.CONCLUSION The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women

BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.

Beta-HCG Levels and Ovarian Ultrasonography Results among Non-Pregnant Women of Reproductive Age in Port Harcourt, Nigeria: A Cross-Sectional Study

Background: Certain ovarian cancers that were previously common in postmenopausal women are now increasingly observed in women of reproductive age. The research on using β-HCG as a diagnostic biomarker for ovarian cancer in women of reproductive age is ongoing. Aim: This study assessed the level of serum β-HCG in non-pregnant women of reproductive age and determined its potential association with suspicious ovarian ultrasonography results. Methods: The study was conducted in Port Harcourt, Nigeria. This study adopted a cross-sectional design on a quota sample of 224 case notes of women aged 18 - 40 years obtained from eight diagnostic centres. A data extraction form was used for data collection. Data analysis employed descriptive statistics, Chi-square, Fisher’s exact test, and Odds Ratio at 95% confidence and 5% significance levels. Results: About 5.8% of the participants exhibited detectable levels of serum β-HCG above 5 IU/L (World Health Organization reference) at a mean concentration of 5.87 (±1.75) IU/L. About 4.0% of the participants had suspicious ovarian lesions identified through ultrasonography. Participants with elevated serum β-HCG levels above the WHO reference were 59 times more likely to have suspicious ovarian lesions (Odds ratio: 59.4, 95%CI: 12.3 - 287.8, p β-HCG level and age (p = 0.041) as well as parity (p Conclusion: Serum β-HCG levels above the WHO reference in non-pregnant women were associated with suspicious ovarian lesions. More rigorous primary research, systematic reviews, and meta-analyses are needed to confirm the findings of this study.

New Progress of CA125 Surveillance in Diagnosis and Treatment of Ovarian Cancer

The fatality rate of ovarian cancer (OC) is the highest, and the 5-year survival rate is only 50.8%. For more than 40 years, CA125 has been the most concerned and widely used biomarker of OC in clinical practice. In recent years, many researchers have proposed a reliable strategy of multiple markers combined with CA125 to screen OC to make up for the lack of accuracy of CA125, redefine the biochemical recurrence threshold of CA125, and use mathematical model scores to provide help for the feasibility of treatment and survival prognosis. To fully understand the role of CA125 in OC screening, initial treatment, and recurrence prediction, and summarize the limitations of CA125, this review has summarized the new progress of CA125 in the diagnosis and treatment of OC in recent years which can also provide a reference for clinicians.

EFFECTS OF TNF ALONE OR IN COMBINATION WITH CHEMOTHERAPEUTIC AGENTS ON HUMAN OVARIAN CANCERS IN VITRO AND IN NUDE MICE

Using the tetrazolium (MTT) assay, we examined the cytotoxicities of recombinant human tumor necrosis factor (rhTNF) and five chemotherapeutic agents, namely CTX, 5-FU, VCR, DDP and KSM, on human ovarian cancer cell lines OVCAR3 and CAOV3. The results showed that the cytotoxicities of rhTNF at concentrations of 50-50 000 U / ml on OVCAR3 cell line and CAOV3 cell line exposed to rhTNF for 24 hours were from 14.2% ± 6.8% to 67.2%± 3.0% and from 8.2%± 4.3% to 60.9%±1.3%, respectively. The cytotoxicities of all five chemotherapeutic agents tested on the two cell lines were much lower than that of rhTNF. We also studied the combined antitumor potential of rhTNF with the five chemotherapeutic agents and the results showed that there were various degrees of synergism in cytotoxicities of rhTNF in combination with DDP or KSM on the two cell lines. Based on experiments in vitro, the in vivo antitumor activities of rhTNF, both alone and in combination with KSM, were examined in OVCAR3 cancer transplanted in nude mice. The results showed a considerable antitumor effect of rhTNF when it was used alone and a marked synergistic effect when it was used in combination with KSM on the xenograft tumors.

Combination of docetaxel-carboplatin for adjuvant chemotherapy of epithelial ovarian,primary peritoneal and fallopian tube cancers:a meta-analysis

Objective： The aim of this study was to compare the efficacies and safeties of the combination of docetaxel- carboplatin with the combination of non docetaxel-carboplatin as first-line chemotherapy for advanced epithelial ovarian, pri- mary peritoneal or fallopian tube cancers. Methods： Relevant articles were identified from MEDLINE （1993-2010）, EMBASE （1980-2010）, MEDION, the Cochrane library, Science Citation Index Expanded databases, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 5 relevant primary studies （1430 women）. Data was extracted for study characteristics and quality. Bivariate random-effect model meta- analysis was used to estimate diagnostic accuracy of the various index tests. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available studies. Results： The frequency of the subgroup analysis of toxicity showed that toxicity action of combination of docetaxel-carboplatin was more severe than that of non docetaxel- carboplatin group （OR = 1.33, 95% CI = 1.13-1.56, P = 0.0005）, whereas that of clinical responses was equivalent in com- parison combination of docetaxel-carboplatin with combination of paclitaxel-carboplatin or docetaxel-cisplatin （OR = 1.0, 95% CI = 0.87-1.16, P = 0.95）. There were heterogeneity （X2 = 79.36, P 〈 0.00001） and inconsistency （83.6%） in toxicity analysis among the trials, while neither heterogeneity （x2 = 3.21, P = 0.99） nor inconsistency （F = 0%） in clinical responses among the trials. Conclusion： The safety of combination of docetaxel-carboplatin is less than that of combination of paclitaxel- carboplatin or docetaxel-cisplatin. However, the clinical responses of combination of docetaxel-carboplatin are comparable with combination of paclitaxel-carboplatin or docetaxel-cisplatin.

Drug repositioning of disulfiram induces endometrioid epithelial ovarian cancer cell death via the both apoptosis and cuproptosis pathways

Various therapeutic strategies have been developed to overcome ovarian cancer.However,the prognoses resulting from these strategies are still unclear.In the present work,we screened 54 small molecule compounds approved by the FDA to identify novel agents that could inhibit the viability of human epithelial ovarian cancer cells.Among these,we identified disulfiram(DSF),an old alcohol-abuse drug,as a potential inducer of cell death in ovarian cancer.Mechanistically,DSF treatment significantly reduced the expression of the anti-apoptosis marker Bcell lymphoma/leukemia-2(Bcl-2)and increase the expression of the apoptotic molecules Bcl2 associated X(Bax)and cleaved caspase-3 to promote human epithelial ovarian cancer cell apoptosis.Furthermore,DSF is a newly identified effective copper ionophore,thus the combination of DSF and copper was used to reduce ovarian cancer viability than DSF single treatment.Combination treatment with DSF and copper also led to the reduced expression of ferredoxin 1 and loss of Fe-S cluster proteins(biomarkers of cuproptosis).In vivo,DSF and copper gluconate significantly decreased the tumor volume and increased the survival rate in a murine ovarian cancer xenograft model.Thus,the role of DSF revealed its potential for used as a viable therapeutic agent for the ovarian cancer.

LncRNA CACNA1G-AS1 up-regulates FTH1 to inhibit ferroptosis and promote malignant phenotypes in ovarian cancer cells

Previous study revealed that ferritin heavy chain-1(FTH1)could regulate ferritinophagy and affect intracellular Fe^(+)content in various tumors,while its N6-methyladenosine(m6A)RNA methylation was closely related the prognosis of ovarian cancer patients.However,little is known about the role of FTH1 m6A methylation in ovarian cancer(OC)and its possible action mechanisms.In this study we constructed FTH1 m6A methylation regulatory pathway(LncRNA CACNA1G-AS1/IGF2BP1)according to related bioinformatics analysis and research,through clinical sample detections we found that these pathway regulatory factors were significantly up-regulated in ovarian cancer tissues,and their expression levels were closely related to the malignant phenotype of ovarian cancer.In vitro cell experiments showed that LncRNA CACNA1G-AS1 could up-regulate FTH1 expression through IGF2BP1 axis,thus inhibited ferroptosis by regulating ferritinophagy,and finally promoted proliferation and migration in ovarian cancer cells.Tumor-bearing mice studies showed that the knock-down of LncRNA CACNA1G-AS1 could inhibited the tumorigenesis of ovarian cancer cells in vivo condition.Our results demonstrated that LncRNA CACNA1G-AS1 could promote the malignant phenotypes of ovarian cancer cells through FTH1-IGF2BP1 regulated ferroptosis.

MiR-194-5p suppresses the warburg effect in ovarian cancer cells through the IGF1R/PI3K/AKT axis

Background:The Warburg effect is considered as a hallmark of various types of cancers,while the regulatory mechanism is poorly understood.Our previous study demonstrated that miR-194-5p directly targets and regulates insulin-like growth factor1 receptor(IGF1R).In this study,we aimed to investigate the role of miR-194-5p in the regulation of the Warburg effect in ovarian cancer cells.Methods:The stable ovarian cell lines with miR-194-5p overexpression or silencing IGF1R expression were established by lentivirus infection.ATP generation,glucose uptake,lactate production and extracellular acidification rate(ECAR)assay were used to analyze the effects of aerobic glycolysis in ovarian cancer cells.Gene expression was analyzed by quantitative polymerase chain reaction(qPCR)and western blot.Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancer tissues.Results:Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATP generation,glucose uptake,lactate production,and ECAR and inhibits both the mRNA and protein expression of PKM2,LDHA,GLUT1,and GLUT3.While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway,whose activation can sustain aerobic glycolysis in cancer cells,and the knockdown of miR-194-5p expression promoted the activation of the PI3K/AKT pathway.Conclusion:Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKT pathway,which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.

Synchronous endometrial and ovarian cancer: A case report

BACKGROUND Synchronous endometrial and ovarian cancer(SEOC)is a rare genital tract tumor.Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer(EC)or OC.In this review we present 2 cases of women who were diagnosed with SEOC,and discuss the clinical characteristic of SEOC,diagnostic and molecular profiling issues.Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples.CASE SUMMARY In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC.They underwent surgical treatment and staging.Next-generation sequencing of 10 gene-panel identified CTNNB1,PIK3CA,and PTEN gene mutations in ovarian tissue in one case,while none of these genes were mutated in other case.Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage.CONCLUSION Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.