Tumor cell SPTBN1 inhibits M2 polarization of macrophages by suppressing CXCL1 expression.

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2-type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non-erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/-  mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription-quantitative real-time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA-MB-231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA-MB-231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic-nuclear protein isolation experiments and ChIP-qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2-type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.

A Reinterpretation of Paracolpium in Radical Hysterectomy: New Insights into Its Surgical Implication.

OBJECTIVE: To reinterpret the surgical anatomy of paracolpium in radical hysterectomy and to explore its implications for the surgery. SETTING: The term "paracolpium" first defined by Fothergill in 1907, is essential in radical hysterectomy. However, several challenges remain unresolved. These include: (1) inconsistent terminology in relation to its defined attributes; (2) the lack of consensus on anatomical landmarks; (3) unclear associations with the cardinal and sacral ligaments; and (4) the critical implications and requirements of paracolpium resection in radical hysterectomy practices. PARTICIPANTS: A patient in her 60s diagnosed with stage IB2 cervical cancer was enrolled in a clinical trial and assigned to the laparoscopic surgery group. A step-by-step, narrated video demonstration. INTERVENTIONS: During the procedure, post-excision of the uterosacral, cardinal, and vesicovaginal ligaments, we identified a ligament-like structure situated between the middle third of the vagina and the pelvic wall. We have termed this structure the "paracolpium ligament." A detailed anatomical description was performed, outlining its crucial attachments: • Medial attachment: middle third of the vagina • Lateral attachment: tendinous arch of the pelvic fascia (TAPF) • Cranial attachment: cardinal-uterosacral ligaments confluence • Caudal attachment: pubococcygeus muscle fascia • Dorsal: paravaginal space • Ventral: pararectal space To ensure a safe dissection, the paracolpium ligament was exposed by removing anterior and posterior fat tissue. The extent of surgical resection was adapted based on the tumor's location. Extensive resection of the paracolpium ligament was essential when the tumor was localized to one side of the vagina to ensure complete removal of the disease; otherwise, preservation of the ligament was considered feasible. CONCLUSION: In this video, we meticulously name and define the "paracolpium ligament," providing groundbreaking insights into its anatomical and surgical implications in radical hysterectomy. Our findings contribute to a better understanding of surgical anatomy for cervical cancer.

CD47-a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features.

BACKGROUND: Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC. METHODS: Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan-Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis. RESULTS: CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732-0.822). The calibration curve showed good consistency. CONCLUSION: CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.

Novel predictors for identifying cervical minimal deviation adenocarcinoma patients with poor prognosis: a long-term observational study in a tertiary centre.

PURPOSE: To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. METHODS: This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. RESULTS: Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5-8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. CONCLUSION: Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis.

Blocking CD47-SIRPα Signal Axis as Promising Immunotherapy in Ovarian Cancer.

Among the three primary gynecological malignancies, ovarian cancer has the lowest incidence but the worst prognosis. Because of the poor prognosis of ovarian cancer patients treated with existing treatments, immunotherapy is emerging as a potentially ideal alternative to surgery, chemotherapy, and targeted therapy. Among immunotherapies, immune checkpoint inhibitors have been the most thoroughly studied, and many drugs have been successfully used in the clinic. CD47, a novel immune checkpoint, provides insights into ovarian cancer immunotherapy. This review highlights the mechanisms of tumor immune evasion via CD47-mediated inhibition of phagocytosis and provides a comprehensive insight into the progress of the relevant targeted agents in ovarian cancer.

A Vascular Centered Surgical Approach to Radical Hysterectomy: Laparoscopic Anatomy of Pelvic Vascular System Revisited.

OBJECTIVE: As a standard therapy for locally invasive cervical cancer, radical hysterectomy (RH) has been in routine medical practice for more than a century [1]. However, challenges still exist due to the troublesome bleeding during parametrium dissection and resection, which could increase the risk of surgical complications and may probably affect surgical outcomes ultimately [2]. This video illustrated the three-dimensional anatomy of the pelvic vascular system with particular emphasis on "deep uterine vein" and further introduced a vascular-centered surgical approach to performing RH, which could facilitate parametrium dissection with less blood loss and obtain enough resection margins. DESIGN: A step-by-step, narrated video demonstration SETTING: A university hospital INTERVENTIONS: After systemic pelvic lymphadenectomy, ureter was then identified along the medial leaf of the broad ligament. By continuously exploring the pelvic cavity along the ureter, communicating branches of the uterine artery to the ureter, urinary bladder, corpus uteri, uterine cervix, and upper vagina were clearly identified in a cranial to caudal direction, demonstrating the arterial network surrounding the urinary system. Coagulating and cutting these blood vessels could free the ureter from retroperitoneum and subsequently excavate the ureteral tunnel easily. Next, a precise dissection of the area below the ureter revealed the whole distribution of currently named "deep uterine vein". Originated from an internal iliac vein, it is much more like a venous confluence than an accompanying vein, with branches crossing directly into the bladder, dorsally to the rectum, and traveling caudally to the anterolateral side of the uterus and vagina in a crisscross fashion, which mandates us to describe it as pampiniform-like venous plexus instead of "deep uterine vein" due to its anatomical distribution and function. Finally, after complete exposure of venous network, enough extent of parametrium could be adequately separated and resected by accurate coagulation of blood vessels on an individualized requirement. CONCLUSION: Recognizing the precise anatomy of pelvic vascular system, especially the entire distribution of currently named "deep uterine vein" and isolating the venous branches connecting to all three parts of parametrium, are key to the RH procedure. Careful attention to the complex vascular anatomy is critical to reducing intraoperative bleeding and avoiding complications in RH.

Cytoreductive surgery is feasible in patients with limited regional platinum-resistant recurrent ovarian cancer.

INTRODUCTION: To evaluate the efficacy of cytoreductive surgery versus chemotherapy for the treatment of limited regional, platinum-resistant ovarian cancer (PROC). MATERIALS AND METHODS: The clinical records of all patients with PROC treated in our center between March 2015 and March 2022 were retrospectively reviewed. We compared the oncology outcomes of patients who received cytoreduction or chemotherapy alone at relapse and presented information about postoperative adjuvant chemotherapy. RESULTS: Among 52 patients with limited regional recurrence, 40.4% (21/52) underwent cytoreduction because of platinum resistance, and 59.6% (31/52) received chemotherapy alone. No residual disease (R0) was achieved in 20 patients (95.2%). The severe morbidity rate within 30 days after the surgery was 15%. The median follow-up was 70.6 months. Compared with the chemotherapy alone group, the surgery group with R0 had better progression-free survival (PFS) (10.6 vs. 5.1 months; hazard ratio (HR) = 0.421; P = 0.0035) and post-relapse survival (PRS) (32.6 vs. 16.3 months; HR = 0.478; P = 0.047), but there was no difference in overall survival (OS) between the two groups. Laparoscopy is associated with lesser intraoperative blood loss with no differences in survival and postoperative complications compared to the open approach (P = 0.0042). Subgroup survival analysis showed that compared with chemotherapy alone, surgery prolonged PFS in patients regardless of tumor size (greater than or equal to 4 cm or less). Surgery group patients who achieved R0 had an objective response rate (ORR) of 36.8% (7/19), among whom 40% (4/10) received platinum rechallenge chemotherapy and 33.3% (3/9) were administered non-platinum chemotherapy. CONCLUSION: When well-selected PROC patients with limited regional recurrence achieved R0, their outcomes were superior to those of patients who received only chemotherapy with an acceptable morbidity rate. Laparoscope technology could be a reliable alternative surgical approach. The reintroduction of platinum agents may be considered following surgery. Further analyses in a larger population are warranted to elucidate the risks and benefits of this surgery and adjuvant chemotherapy strategy.

Depletion of UBE2C reduces ovarian cancer malignancy and reverses cisplatin resistance via downregulating CDK1.

Ovarian cancer is the most lethal gynecological malignancy, but the mechanisms of ovarian cancer progression and cisplatin resistance remain unclear. Emerging evidence suggested that ubiquitin-conjugating enzyme E2C (UBE2C) was highly expressed in a variety of tumors and acted as an oncogene. In our study, we demonstrated that UBE2C was overexpressed in ovarian cancer by immunohistochemistry (IHC) and The Cancer Genome Atlas (TCGA) database analysis. It was also found that high levels of UBE2C expression predicted worse clinical outcomes in ovarian cancer. After knocking down UBE2C, SKOV3 and A2780 cells showed inhibitory cell proliferation, increased apoptosis by blocking G2/M transition in vitro and in vivo. Besides, the downregulation of UBE2C reversed the cisplatin resistance states of SKOV3/DDP and A2780/DDP cells. Interestingly, CDK1 expression was also downregulated in UBE2C depleted ovarian cancer cells. Furthermore, we found that UBE2C expression was highly correlated with CDK1 expression in ovarian cancer tissues and cell lines, indicating that UBE2C might cooperate with CDK1 in ovarian tumorigenesis. Collectively, our findings strongly supported UBE2C as a candidate oncogene and a potential target for the treatment of ovarian cancer.

Endometrioid endometrial cancer "recurring" as high-grade serous adenocarcinoma in the inguinal lymph nodes in a patient with germline MLH1 mutated Lynch syndrome: consequence or coincidence?

BACKGROUND: Inguinal metastasis of endometrial cancer (EC) is rare. The aims of the study were to identify whether the inguinal metastatic tumor was originated from EC and to present the management of the disease. METHODS: The clinical data of a case of endometrioid EC "recurring" as serous adenocarcinoma in the inguinal lymph nodes were collected and analyzed. Paired samples of primary and metastatic tumors were used for exome sequencing to determine whether the tumors are same origination and to identify potential gene mutations associated with the relapse. RESULTS: The patient presented with right inguinal lymphadenopathy and histopathology revealed metastatic serous adenocarcinoma. A germline MLH1 mutation was identified. A combination of bioinformatical methods and cancer-related gene exome sequencing assay identified that only 17 (0.1%) somatic gene mutations were shared by the primary EC and the metastatic inguinal tumor, suggesting that the metastasis did not originate from the primary EC. Postoperative radiation therapy followed by a combination of chemotherapy were performed. Thirty-four months after that, the patient was doing well without any evidence of recurrence. CONCLUSIONS: This is the first case of metastatic inguinal serous adenocarcinoma in a woman with Lynch syndrome shortly after surgical treatment of stage I endometrioid EC.

Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor.

BACKGROUND: The tumour microenvironment conferred by mesenchymal stem cells (MSCs) plays a key role in tumour development and progression. We previously determined that platelet-activating factor receptor (PAFR) was overexpressed in ovarian cancer cells (OCCs) and that PAF can promote ovarian cancer progression via PAF/PAFR-mediated inflammatory signalling pathways. Evidence suggests that MSCs can secrete high concentrations of PAF. Here, we investigated the role of PAF/PAFR signalling in the microenvironment mediated by MSCs and OCCs and its effect on cancer progression. METHODS: The PAF concentrations in the culture media of MSCs, OCCs and co-cultured MSCs and OCCs were determined by ELISA. The effects of MSCs on OCCs in vitro were assessed on cells treated with conditioned medium (CM). The expression and phosphorylation of key proteins in the PAF/PAFR signalling pathway were evaluated. In vivo, MSCs/RFP and SKOV3 cells were co-administered at different proportions to nude mice by interscapular injection. Mice in the WEB2086 group were intraperitoneally injected with the PAFR antagonist WEB2086 at a dose of 1 mg/kg.d for the duration of the animal experiments. Tumour progression was observed, and the weight and survival time of mice were measured. The PAF concentration in peripheral and tumour site blood was determined by ELISA. RESULTS: High concentrations of PAF were detected in CM from MSCs and MSCs co-cultured with OCCs. Both types of medium promoted non-mucinous OCC proliferation and migration but had no effect on mucinous-type OCCs. These effects could be blocked by PAFR inhibitors. The expression and phosphorylation of key proteins in the PAF/PAFR pathway significantly increased upon treatment with PAF and MSC-CM. In vivo, the tumour volume was larger following co-injection of SKOV3 cells and MSCs/RFP than following injection of SKOV3 cells alone. The tumour-promoting effect of MSCs/RFP was blocked by the PAFR antagonist WEB2086. Serum PAF concentrations significantly increased in co-injected mice. CONCLUSION: Our results suggest that the tumour-promoting effect of MSCs on OCCs via their cross-talk in the tumour microenvironment was, at least in part, mediated by the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer.

Establishment of Patient-Derived Tumor Xenograft Models of High-Risk Endometrial Cancer.

OBJECTIVE: High-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models. METHODS: Fresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors. RESULTS: The total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts. CONCLUSIONS: The combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.

Constructing predictive models for vaginal surgery in patients with noninvasive gynecological conditions.

OBJECTIVE: To develop predictive models for vaginal operative route selection based on clinical variables that can be easily assessed preoperatively in patients with noninvasive gynecological conditions. DESIGN: Retrospective study. SETTING: University Hospital. POPULATION: Women with routine gynecological surgeries via different approaches. METHODS: The medical records of 315 women without prolapse and undergoing hysterectomy, adnexal cystectomy or myomectomy were reviewed. Multiple logistic regression analysis was used to identify factors associated with the vaginal approach for each procedure. Predictive models were generated and optimal cut-off points were identified using the receiver operating characteristic curve. MAIN OUTCOME MEASURES: Predictive models for different vaginal surgical procedures. RESULTS: For hysterectomy, the patient's body mass index, dysmenorrheal complaints and uterine size were identified as negative predictors for vaginal hysterectomy, whereas previous vaginal delivery was positive. For adnexal cystectomy, adnexal pathology was a negative predictor, whereas previous vaginal delivery and ovarian cyst size were positive. For myomectomy, the body mass index and number of fibroids were negative predictors while previous vaginal delivery was positive. All three models were able to predict the vaginal procedures undergone by women and the areas under the curve were 0.88, 0.95 and 0.92, respectively. Each optimal model cut-off value (logit(p) = 0.53, 0.36, 0.73) resulted in good sensitivity (92.3%, 100% and 87.5%, respectively) and specificity (77.8%, 88.6% and 90.9%, respectively). CONCLUSION: These predictive models, which used clinical variables that can be easily assessed preoperatively, may help surgeons to select candidates for different vaginal procedures.

A randomized controlled trial to compare short-term outcomes following infragastric and infracolic omentectomy at the time of primary debulking surgery for epithelial ovarian cancer with normal-appearing omentum.

BACKGROUND: Omentectomy is an important procedure in surgery for epithelial ovarian cancer, but the scope of omentectomy is not recommended in the guidelines. This study was performed to evaluate the benefits and risks of infragastric omentectomy in patients with epithelial ovarian cancer. METHODS: This trial is a single center prospective study. Primary epithelial ovarian cancer patients with normal-appearing omentum were randomly assigned to either the control or experimental group and underwent infracolic or infragastric omentectomy, respectively. The primary endpoint was progression-free survival. This trial is registered on Chinese clinical trial registry site (ChiCTR1800018771). RESULTS: A total of 106 patients meeting the inclusion criteria for ovarian cancer were included during the study period. Of these, 53 patients underwent infracolic omentectomy, whereas 53 patients received infragastric omentectomy. Multivariate analysis revealed that infragastric omentectomy could improve the detection rate of omental metastases (OR: 6.519, P = 0.005). Infragastric omentectomy improved progression-free survival significantly for those cases with higher than stage IIB disease (HR: 0.456, P = 0.041). Based on the short-term results, infragastric omentectomy did not cause more perioperative complications. CONCLUSIONS: Compared with infracolic omentectomy, infragrastric omentectomy may be a more appropriate surgical procedure for stage IIB-IIIC epithelial ovarian cancer patients with normal-appearing omentum.

Advancing Ovarian Cancer Therapeutics: The Role of Targeted Drug Delivery Systems.

Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.

Unraveling the molecular mechanisms of lymph node metastasis in ovarian cancer: focus on MEOX1.

BACKGROUND: Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome. RESULTS: Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells. CONCLUSIONS: The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.