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

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World Journal of Clinical Oncology 2025年第1期16卷 43-52页

作者： Zhi-Jian Tang Yuan-Ming Pan Wei Li Rui-Qiong Ma Jian-Liu Wang department of obstetrics and gynecology Peking University People’s HospitalBeijing 100044China Cancer Research Center Beijing Chest HospitalBeijing 101149China department of thoracic Surgery Sichuan Provincial People's HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment *** To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural *** Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from the Cancer Genome Atlas and Gene Expression *** genes were sourced from the MitoCarta3.0 *** discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation *** 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 *** In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy *** 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 *** 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 *** 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.

关键词： Ovarian cancer Mitochondria Prognosis Immunotherapy Neural network

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Protective Effect and Mechanism of Kuntai Capsule on Angiotensin II-Induced Hypertension in Ovariectomized Rats

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Chinese Journal of Integrative Medicine 2023年第6期29卷 526-533页

作者： GE Xiao-fen LI Sha-sha LIU Yan-hua LU Mei-qiu SU Hui-na YANG Xin SUN Xiao-wan department of obstetrics and gynecology Peking University People's HospitalBeijing(100044)China department of obstetrics and gynecology Dongying People's HospitalDongyingShandong Province(257000)China

Objective To explore the protective effect and mechanism of Kuntai(KT)Capsule on angiotensin II(Ang II)-induced hypertension in ovariectomized(OVX)*** Fifty-four rats were randomly divided into 6 groups according to a random number table,9 in each group:control,OVX sham+Ang II,OVX,OVX+Ang II,OVX+Ang II+E2,and OVX+Ang II+*** rats model was constructed by retroperitoneal bilateral *** 4 weeks of pretreatment with KT Capsule[0.8 g/(kg·d)and 17-β-estradiol(E2,1.2 mg/(kg·d)]respectively,Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat *** pressure of rat tail artery was measured in a wake state of rats using a non-invasive *** pressure changes were compared between the intervention groups(OVX+Ang II+KT,OVX+Ang II+E2)and the negative control group(OVX+Ang II).Serum malondialdehyde(MDA)level and superoxide dismutase(SOD)activity were detected *** expressions of oxidative stress-related protein superoxide dismutase2(SOD2)and anti-thioredoxin(TRX),autophagy marker protein[beclin1,light chain(LC)3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase(PI3K)/serine/threonine kinase(AKT)-mammalian target of rapamycin(mTOR)]were evaluated by Western *** Compared with the OVX+Ang II group,the systolic blood pressure of OVX+Ang II+KT group was significantly lowered(Pthe diastolic blood ***,SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II+KT group compared with the OVX+Ang II group(Pthe OVX+Ang II+KT group,respectively(Pth OVX+Ang II group,the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II+KT group were also up-regulated(Pthe expression levels of p-PI3K,p-AKT and mTOR protein were down-regulated(P<0.05).Conclusion KT could protect blood pr

关键词： Kuntai Capsule Chinese medicine perimenopausal hypertension angiotensin II

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Oncogenic role of Tc17 cells in cervical cancer development

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World Journal of Clinical Cases 2020年第1期8卷 11-19页

作者： Zun-Sheng Zhang Ying Gu Bing-Gang Liu Hong Tang Yu Hua Jun Wang department of obstetrics and gynecology Shanghai Seventh People’s Hospital

BACKGROUND As one of the subsets of CD8+T cells,Tc17 cells have recently been identified and are characterized by the secretion of interleukin(IL)-17,which is related to inflammatory *** To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer *** Flow cytometry assay,immunohistochemistry,and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical *** to cell suspension culture,ELISA was carried out to measure the production of IL-6,IL-1β,IL-23,CXCL12,and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical *** addition,multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards *** Compared with normal tissues,Tc17 cells specifically accumulated in tumor tissues of cervical cancer *** cells produced a greater amount of IL-6,IL-1β,and IL-23,which in turn promoted Tc17 cell *** the traditional cytotoxic CD8^+T cells,Tc17 cells secreted IL-17,which subsequently promoted CXCL12 expression in tumor cells,eventually enhancing the proliferation and migration of tumor ***,the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical *** Our data identified the oncogenic role of Tc17 cells in the development of cervical *** propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.

关键词： Cervical cancer Tc17 cells Interleukin-17 Cancer development Biological function Oncogenic role

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Gasless laparoscopy for benign gynecological diseases using an abdominal wall-lifting system

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2009年第11期10卷 805-812页

作者： Yue WANG Heng CUI Yan ZHAO Zhi-qi WANG department of obstetrics and gynecology Peking University People's Hospital Beijing 100044 China

Objectives: the use of gasless laparoscopy with an abdominal wall-lifting device for benign gynecological diseases was compared to conventional laparoscopy with CO2 pneumoperitoneum. Methods: From February 2007 to July 2007,76 women with uterine and/or adnexal benign diseases and candidates for laparoscopic surgery were recruited in this study. thirty-two women underwent gasless laparoscopic surgery and 44 women underwent pneumoperitoneum laparoscopic surgery. Results: Diverse pathologies,including adnexal cyst,uterine myoma and ectopic pregnancy,were treated successfully with gasless laparoscopic surgery. Compared with the patients in the pneumoperitoneum group,the similar hospital stay (P=0.353) and intraoperative blood loss (P=0.157) were observed. However,the mean operative time in the gasless group was significantly longer than that in the pneumoperitoneum group (P=0.003). No severe intraoperative or postoperative complications were found in either group,except for one case of laparotomic conversion in the pneumoperitoneum group due to dense pelvic adhesions. the total hospital charges were significantly less in the gasless group than in the pneumoperitoneum group (P=0.001). In 38 cases of ovarian cyst resection,the mean operative time in the gasless group remained longer than that in the pneumoperitoneum group (P=0.017). the total hospital charges were also significantly less in the gasless group than in the pneumoperitoneum group (Pthat the laparoscopic procedure using the gasless technique was a safe,effective method to treat benign gynecological diseases. Moreover,it was easy to master. As a minimally invasive treatment,gasless laparoscopic surgery provides a good choice to patients in the undeveloped regions in China without increasing the patients’ and the government’s burden significantly.

关键词： Gasless laparoscopy Pneumoperitoneum laparoscopy Ovarian cyst resection

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

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BIOCELL 2024年第8期48卷 1265-1273页

作者： SHAN JIANG XIUFENG LIN YANFEI CHEN XINNING LI JIALI KANG department of gynecology and obstetrics The First Affiliated Hospital of Jinan UniversityGuangzhou510180China Reproductive Medical Center Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China department of gynecology and obstetrics Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China department of gynecology and obstetrics Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhou510180China

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor *** 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 ***,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still ***: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 *** assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer *** pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer ***:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian *** 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 ***,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.

关键词： Ultra-conserved non-coding RNA uc.243 Drug efflux Drug transporters Chemoresistance Ovarian cancer

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Up-regulation of mitochondrial antioxidation signals in ovarian cancer cells with aggressive biologic behavior

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第5期12卷 346-356页

作者： Yue WANG Li DONG Heng CUI Dan-hua SHEN Ying WANG department of obstetrics and gynecology People's Hospital Peking University Beijing 100044 China department of obstetrics and gynecology Beijing Jishuitan Hospital Peking University Beijing 100035 China department of Pathology People's Hospital Peking University Beijing 100044 China

Objective： Recently, a high frequency of mutations in mitochondrial DNA （mtDNA） has been detected in ovarian cancer. To explore the alterations of proteins in mitochondria in ovarian cancer, a pair of human ovarian carcinoma cell lines （SKOV3/***1） with different metastatic potentials was examined. Methods： Cancer cells *** were derived from the ascitic tumor cells of nude mice bearing a tumor of ovarian cancer cells SKOV3. *** exhibited a higher degree of migration potential than its paired cell line SKOV3. the proteins in the mi- tochondria of these two cells were isolated and separated by 2-D gel electrophoresis. the differently expressed proteins were extracted and identified using matrix assisted laser desorption ionisation/time-of-flight/time-of-flight （MALDITOF/TOF）, and finally a selected protein candidate was further investigated by immunohistochemistry （IHC） method in nude mice bearing tumor tissues of these two cells. Results： A total of 35 spots with different expressions were identified between the two cells using 2D-polyacrylamide gel electrophoresis （PAGE） approach. Among them, 17 spots were detected only in either SKOV3 or *** cells. Eighteen spots expressed different levels, with as much as a three-fold difference between the two cells. Twenty spots were analyzed using MALDI-TOF/TOF, and 11 of them were identified successfully; four were known to be located in mitochondria, including superoxide dismutase 2 （SOD2）, fumarate hydratase （FH）, mitochondrial ribosomal protein L38 （MRPL38）, and mRNA turnover 4 homolog （MRTO4）. An increased staining of SOD2 was observed in *** over that of SKOV3 in IHC analysis. Conclusions： Our results indicate that the enhanced antioxidation and metabolic potentials of ovarian cancer cells might contribute to their aggressive and metastatic behaviors. the underlying mechanism warrants further study.

关键词： Ovarian carcinoma Mitochondria Invasion Proteomic Superoxide dismutase 2 (SOD2)

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Influence of gonadotropin-releasing hormone agonist on the effect of chemotherapy upon ovarian cancer and the prevention of chemotherapy-induced ovarian damage:an experimental study with nu/nu athymic mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第11期13卷 894-903页

作者： Qiong-yan LIN Yi-feng WANG Hui-nan WENG Xiu-jie SHENG Qing-ping JIANG Zhi-ying YANG department of obstetrics and gynecology Key Laboratory for Major Obstetric Diseases of Guangdong Province the Third Affiliated Hospital of Guangzhou Medical University Guangzhou 510150 China department of obstetrics and gynecology Zhujiang Hospital Nanfang Medical University Guangzhou 510282 China

Background and objective:Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage. Methods:nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). Results:Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (Pthere was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (Pthe extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin

关键词： Gonadotrophin-releasing hormone Cisplatin Ovarian cancer Animal experiment

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Highly specific selenium nanosystems for fluorescent image-guided rapid diagnosis and pathological grading of ovarian malignant tumors

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Chinese Chemical Letters 2023年第5期34卷 433-439页

作者： Shaolie Zheng Wei Huang Nan Li Yuan Shen Xiaoyu Wang Tianfeng Chen department of obstetrics&gynecology The First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

Comprehensive surgical staging or optimal tumor cytoreductive surgery of malignant ovarian cancer directly affects disease ***,a fluorescent selenium nanoparticle(Se@RGD/S2.2)decorated with cancer-targeting Arg-Gly-Asp(RGD)peptides and GCAGTTGATCCTTTGGATACCCTGG aptamer(S2.2)was developed for use as a diagnostic agent to achieve rapid,noninvasive diagnosis and visualization of microinvasive lesions during surgery for malignant ovarian cancer.

关键词： Ovarian cancer Selenium Fluorescence imaging Diagnosis Pathological grading

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Traction force with extracellular matrix mediated by cytoskeleton influences metastasis through SLC8A1 induced Wnt-b-catenin pathway in endometrial cancer

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Genes & Diseases 2024年第5期11卷 98-101页

作者： Xingchen Li Xin Xu Jianliu Wang department of obstetrics and gynecology Peking University People’s HospitalBeijing 100044China department of obstetrics and gynecology Beijing ChaoYang HospitalCapital Medical UniversityBeijing 100020China

Endometrial cancer(EC)is one of the most prominent malignancies in ***,despite these advancements in understanding EC pathogenesis,mortality rates have not *** force(TF)refers to endogenous mechanical forces exerted by cells.1 these forces act on the extracellular matrix and the extracellular tumor microenvironment through focal adhesions,thereby regulating cell proliferation and ***,the TF characteristics of endometrial cancer cells and their heterogeneity remain unclear.

关键词： endometrial metastasis endogenous

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DIFFERENTIAL EXPRESSION OF ADHESION MOLECULES (CD44,CD29,ICAM-1 AND E-CADHERIN) IN OVARIAN CANCER SK-OV-3ip1 CELLS GROWN AS MONOLAYER AND MULTICELLULAR AGGREGATES

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Chinese Journal of Cancer Research 2003年第1期15卷 19-23页

作者：席晓薇陈建利丰有吉万小平谷可军 department of obstetrics and gynecology The Affiliated No. 1 People's Hospital Shanghai Jiaotong University hospital of obstetrics and gynecology

Objective: To detect mRNA levels and expression ofCD44, CD54, CD29 and E-cadherin (E-cad) and to discuss their relationship with formation and drug resistance ofovarian cancer SKOV3ip1 multicellular ***: Liquid overlay system was employed to obtainmulticellular aggregates. mRNA levels and expression ofCD44, CD54, CD29 and E-cad were investigated with RTPCR and flow cytometry (FCM) respectively. Results:Compared with monolayer cells, RT-PCR results showed a decrease in CD44 mRNA level by 0.626-fold and a decrease in CD29 mRNA level by 0.792-fold in multicellularaggregates. However, an increase in CD54 mRNA level by 1.815-fold and an increase in E-cadherin mRNA level by1.344-fold were found in multicellular aggregates. theresults revealed the downregulation of CD44 and CD29 and the upregulation of CD54 and E-cad genes activity. CD44 expression in monolayer cells and multicellular aggregates were 75.995?.046 and 50.700?.351 (%) respectively andthere was a significant decrease in multicellular aggregates (P=0.001). Compared with control cells, no expression of CD54 was detected in monolayer cells (P=0.563) but markedly elevated CD54 expression was detected in multicellular aggregates (15.780?.217) (%) (Pth positive rates of 96.290+1.201 (%) and 92.494?.055 (%). However, the expression of CD29 in multicellular aggregates was significantly reduced (P=0.014). Also no expression of E-cadherin was found in monolayer cells compared with control cells (4.490?.283) (%) (P=0.65) while significantly increased expression in aggregates cells (17.258?5.572) (%) (P=0.003) was observed. Conclusion: Significant differences in mRNA levels and expression of CD44, CD54, CD29 and E-cadherin clearly exist between monolayer cells and multicellular aggregates, which may be associated with the formation of multicellular aggregates and its drug resistance.

关键词： Multicellular aggregates Ovarian neoplasms Adhesion molecules Chemotherapy Drug resistance

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