Epithelial Ovarian Cancer Patients Research Articles

Maximal Effort Cytoreduction in Epithelial Ovarian Cancer: Perioperative Complications and Survival Outcomes from a Retrospective Cohort.

Background: Rates of maximal effort cytoreductive surgery in ovarian cancer patients increase gradually the last decade. The purpose of the present study is to evaluate factors that contribute to survival and morbidity outcomes in this group of patients. Methods: We retrospectively reviewed patient records of epithelial ovarian cancer patients with an intermediate and high Mayo Clinic surgical complexity score, operated between January 2010 and December 2018. Results: Overall, 107 patients were enrolled in the present study with a median age of 62 years (23-84) and a follow-up of 32 months (2-156). Thirteen Clavien-Dindo grade IIIa complications were documented in 10 patients (9.3%). Of all the investigated factors, only stage IVb (p = 0.027) and interval debulking surgery (p = 0.042) affected overall survival rates. Overall survival outcomes of patients operated on a primary setting started to differentiate compared to those that received neo-adjuvant chemotherapy after the 4th postoperative year. Conclusions: Maximal effort cytoreductive procedures should be considered feasible in the modern surgical era, as they are accompanied by acceptable rates of perioperative morbidity. Hence, every effort should be made to perform them in the primary setting, rather than following neoadjuvant chemotherapy as current evidence favor increased survival rates of patients that will likely surpass an interval of observation of more than 4 years.

Long noncoding RNA FTX promotes epithelial-mesenchymal transition of epithelial ovarian cancer through modulating miR-7515/TPD52 and activating Met/Akt/mTOR.

Overexpressed long noncoding RNA FTX is associated with low survival rate of epithelial ovarian cancer (EOC) patients, and enhances tumor infiltration. Thus, we aim to illuminate the undefined underlying mechanisms. Real-time quantitative polymerase chain reaction was applied to detect the expressions of FTX, miR-7515, miR-342-3p, miR-940, miR-150-5p, miR-205-5p and tumor protein D52 (TPD52). Cell counting kit-8 and transwell assays were utilized to explore the cell viability, migration or invasion of EOC cells. Western blot was conducted to measure the expressions of E-cadherin, N-cadherin, Met, phosphorylated (p)-Met, Akt, p-Akt, mTOR and p-mTOR. LncBase and TargetScan predicted the binding of miR-7515 with FTX, and the binding of TPD52 with miR-7515, respectively. The two bindings were further validated by dual luciferase reporter assay. As a result, FTX sponged miR-7515 and miR-7515 targeted to TPD52. FTX was overexpressed in four EOC cell lines. Overexpressed FTX enhanced the cell viability, migration or invasion of EOC cells, elevated N-cadherin and TPD52 expressions, phosphorylated Met/Akt/mTOR, and inhibited E-cadherin expression. All these influences were subsequently reversed by miR-7515 mimic. Collectively, FTX regulates miR-7515/TPD52 to facilitate the migration, invasion or epithelial-mesenchymal transition of EOC through activating Met/Akt/mTOR signaling pathway.

Immune environment and antigen specificity of the T cell receptor repertoire of malignant ascites in ovarian cancer.

We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases. TCR clustering was implemented using Grouping of Lymphocyte Interactions by Paratope Hotspots software. Patients with poor prognosis had ascites characterized by an increased ratio of CD8+ T cells to regulatory T cells, which correlated with an increased productive frequency of the top 100 clones and decreased productive entropy. TCRs enriched in patients with an excellent or good prognosis were more likely to recognize cancer antigens and contained more TCR reads predicted to recognize epithelial ovarian cancer antigens. In addition, a TCR motif that is predicted to bind the TP53 neoantigen was identified, and this motif was enriched in patients with an excellent or good prognosis. Ascitic fluid in high-grade epithelial ovarian cancer patients with an excellent or good prognosis is enriched with TCRs that may recognize ovarian cancer-specific neoantigens, including mutated TP53 and TEAD1. These results suggest that an effective antigen-specific immune response in ascites is vital for a good outcome in high-grade epithelial ovarian cancer.

Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues

ObjectiveThe therapeutic effect of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer (EOC) with somatic BRCA mutations is consistent with that observed in patients with germline BRCA mutations, indicating the importance of detecting both germline and somatic BRCA mutations concurrently. We compared the efficacy of multi-gene panel next generation sequencing (NGS) in EOC patients’ formalin-fixed, paraffin-embedded (FFPE) tissue to that of conventional Sanger sequencing in blood samples. Materials and methodsThis study included 48 patients with EOC, and both blood Sanger sequencing and FFPE tissue NGS were conducted in all of them. Clinical and pathological data were reviewed, including age at diagnosis, histology, and stage. Blood Sanger sequencing was performed using peripheral blood leukocytes. The target regions of 90 cancer-related genes were identified using FFPE tissue. ResultsThe median age of patients was 56.1 years, with serous carcinoma (n = 40, 83.3%) and stage III (n = 37, 77.1%) being the most common histology and International Federation of Gynecology and Obstetrics (FIGO) stage, respectively. FFPE tissue NGS identified ten pathogenic variants, including all eight pathogenic variants identified by blood Sanger sequencing and two additional pathogenic variants. Furthermore, FFPE tissue NGS identified 19 variants of uncertain significance (VUS), including all ten VUS identified by blood Sanger sequencing and nine additional VUS. ConclusionThe FFPE tissue multi-gene panel NGS had 100% sensitivity for detecting BRCA germline mutations and could detect additional somatic mutations. Furthermore, performing FFPE tissue multi-gene panel NGS followed by blood Sanger sequencing sequentially may help differentiate germline from somatic BRCA mutations for genetic counseling.

Association of raised CA 125/ CEA ratio and positive Ascitic fluid cytology with diagnosis of ovarian cancer in patients with adnexal mass.

Objective: To look for the association of raised CA 125/ CEA ratio and positive ascitic fluid cytology with the diagnosis of epithelial ovarian cancer in patients with an adnexal mass. Study Design: Comparative Cross-sectional study. Setting: Department of Oncology and Gynecology, Sheikh Zayed Hospital Rahimyarkhan. Period: September 2021 to February 2022. Material & Methods: A total of three hundred patients presenting with adnexal mass were recruited for the study. All patients underwent detailed evaluation, including CA 125 levels, CEA levels and ascitic fluid cytology. After complete staging workup, they underwent surgery and histopathological analysis of adnexal mass. A consultant histopathologist made the diagnosis of ovarian cancer. Association of various factors, including raised CA 125/ CEA ratio and positive ascitic fluid cytology with the diagnosis of ovarian cancer, was established. Results: Out of 350 patients of adnexal mass included in analysis, 273 (88%) were diagnosed with ovarian carcinoma, while 77 (22%) were not diagnosed with ovarian cancer after the surgery and had a diagnosis other than ovarian cancer. 179 (51.2%) patients were post-menopausal whereas 171 (48.8%) were pre-menopausal. It was revealed that raised CA-125/CEA ratio and positive ascitic fluid cytology had a statistically significant association with the diagnosis of ovarian carcinoma on histopathology (p-value<0.001). Conclusion: Most patients who presented with adnexal mass were diagnosed with ovarian carcinoma in our study. Raised CA 125/ CEA ratio and positive ascitic fluid cytology at baseline predicted a histopathological diagnosis of ovarian cancer in our study participants.

Analysis of Erythrocyte Sedimentation Rate Order in Epithelial Ovarian Cancer.

Erythrocyte sedimentation rate order (ESRO), platelet-lymphocyte ratio (PLR), red cell distribution width (RDW), and neutrophil-lymphocyte ratio (NLR) are hematological parameters that reflect the presence of biomarkers in epithelial ovarian cancer (EOC). This study evaluated the best haematological parameter in order to distinguish between EOC patients and healthy individuals. There were a total of 33 patients with EOC as subjects treated in Dr. Sardjito hospital, Yogyakarta, Indonesia and 32 volunteer subjects as controls. Curves of receiver operation, area under the curve, specificity, and sensitivity were estimated. To demonstrate EOC's presence, the ESRO was better than the hematological parameters of RDW, PLR, and NLR (AUC = 0.9245, 0.9010, 0.8351, and 0.7457, respectively; sensitivity and specificity = 83.3 and 90.6; 88.9 and 87.5; 100.0 and 68.8; and 94.4 and 53.1, respectively) at the cut-off points 1,125, 44.2, 163.2, and 2,551. Hence, ESRO is a better parameter to indicate the presence of EOC compared to RDW, PLR and NLR.

Abstract A084: Oncogenic role for upregulated lymphoblastic leukemia derived sequence-1 in the progression of ovarian cancer and its metastasis

Abstract In 2022, about 19,880 women will be newly diagnosed with ovarian cancer (OC), out of which around 12,180 will die. Epithelial Ovarian Cancer (EOC) represents approximately 95% of all OC and is the fifth leading cause of cancer-related deaths in women (deadliest among all gynecological malignancies). Standard treatment for EOC includes surgery, platinum-based chemotherapy, and radiation therapy. Despite these advancements (more than 90% of patients relapse), not all racial and ethnic groups have benefited equally. For instance, the five-year survival rate for OC grew from 33% to 48% among non-Hispanic White women but declined from 44% to 41% among African American (AA) women. The higher tendency to develop chemoresistance in AA women further contributes to their worst survival. No precise mechanisms that contribute to OC racial health disparity have been explained. We aim to delineate the genetic and molecular mechanisms responsible for driving aggressive tumor growth in AA women that disproportionately affect outcomes. This would aid in developing precision therapeutics and eliminate racial disparity in OC outcomes. Analysis of the TCGA data for OC revealed that the Lymphoblastic Leukemia-Derived Sequence 1 (LYL1) gene is one of the frequently amplified genes in OC. About 12% of all the OC shows LYL1 gene amplification. Interestingly, analysis based on ethnicity revealed a remarkable 36% of LYL1 amplification in AA EOC patients, which is one of the top genes after MYC. Importantly, EOC patients with high levels of LYL1 expression (n=202) had a lower survival rate (p=0.003) than those with low levels of LYL1 expression (n=1640). To further confirm the oncogenic functions of LYL1, we analyzed LYL1 expression in EOC cell lines compared to normal fallopian tube epithelial cells (FTECs) and its contribution to OC cell growth and metastatic potential. As expected, LYL1 is upregulated in most of the EOC cell lines compared to normal FTECs, and siRNA-mediated downregulation of LYL1 in EOC cell lines decreased their clonogenic, migration and invasion potential. Conversely, ectopic expression of LYL1 in an EOC cell line expressing low or undetectable levels of LYL1 exhibited increased potential for migration, invasion, and ability to form tumor spheroids. To validate these in vitro studies, we implanted the OVCAR8 cell xenografts transuded with lentivirus-mediated non-targeting shRNAs or shLYL1 into immunocompromised mice. Consistent with the in vitro data, LYL1 expressing OVCAR8 cell xenograft tumors grew aggressively with widespread metastasis in the peritoneum and distant organs. In contrast, LYL1 knockdown tumor xenografts grew slow and showed decreased metastasis. Together, our results show that upregulated or amplified LYL1 in EOC promotes aggressive tumor growth and may contribute to racial disparity in EOC, as this gene is amplified in over 36% of AA OC patients compared to 12% of White patients. Additionally, our studies suggest that LYL1 could be a poor prognostic marker for OC and racial disparities in OC outcomes. Citation Format: Naresh Sah, Swetha Peddibhotla, Bayley Richardson, Pamela Luna, Neel A. Bansal, Chinnadurai Mani, Mark Reedy, Komaraiah Palle. Oncogenic role for upregulated lymphoblastic leukemia derived sequence-1 in the progression of ovarian cancer and its metastasis [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A084.

Identification of two theranostic biomarker panels for epithelial ovarian cancer.

Epithelial Ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. Because the disease is asymptomatic in early-stage, the majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Mediators of tumoral microenvironment may affect EOC progression and resistance to treatment. Analysis of serum proteins to identify a panel of theranostic biomarkers for EOC. Serum levels of 65 analytes were determined in EOC patients, and healthy controls with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. Twenty-one analytes: 7 cytokines (IFN-γ, IL-12p70, IL-13, IL-18 and TSLP), 7 chemokines (Eotaxin, eotaxin-2, IP-10, BLC, I-TAC, SDF-1α, and fractalkine), 2 growth factors (MMP-1, VEGF-α), and 5 soluble receptors (APRIL, CD40L, TWEAK, CD30 and TNFRII; were significantly differentially expressed between the two groups. ROC curves showed that only seven of them (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine, and Tweak) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, five cytokines: IFN-γ, IL-1 β, IL-8, MIP-1β, and TNF-α are positively associated with patients who developed resistance to taxol-platinum-based chemotherapy (CT). This study has revealed a first panel of 7 analytes (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine and Tweak) that can be used for early detection of EOC and a second panel of five cytokines (IFN-γ, IL-1β, IL-8, MIP-1β, TNF-α) that can help clinicians to identify EOC patients who are at higher risk to develop resistance to CT of EOC.

Epithelial Ovarian Cancer Patients and Clinicopathological Features and Survival: A Comparison of Outcomes of Two Age Cohorts in Bangladesh

Epithelial Ovarian Cancer Patients and Clinicopathological Features and Survival: A Comparison of Outcomes of Two Age Cohorts in Bangladesh

Exosomes as Crucial Emerging Tools for Intercellular Communication with Therapeutic Potential in Ovarian Cancer

More than two-thirds of epithelial ovarian cancer (EOC) patients are diagnosed at advanced stages due to the lack of sensitive biomarkers. Currently, exosomes are intensively investigated as non-invasive cancer diagnostic markers. Exosomes are nanovesicles released in the extracellular milieu with the potential to modulate recipient cells' behavior. EOC cells release many altered exosomal cargoes that exhibit clinical relevance to tumor progression. Exosomes represent powerful therapeutic tools (drug carriers or vaccines), posing a promising option in clinical practice for curing EOC in the near future. In this review, we highlight the importance of exosomes in cell-cell communication, epithelial-mesenchymal transition (EMT), and their potential to serve as diagnostic and prognostic factors, particularly in EOC.

A Multiplex Biomarker Assay Improves the Prediction of Survival in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC. Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS. The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05). In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.

Prognostic Value of En-Block Radical Bowel Resection in Advanced Ovarian Cancer Surgery With HIPEC.

To identify prognostic factors of survival and recurrence in advanced ovarian cancer patients undergoing radical surgery and HIPEC. In a single Department of Surgical Oncology, Peritoneal Surface Malignancy Program, and over a 16-year period, from a total of 274 epithelial ovarian cancer patients, retrospectively, we identified 152 patients undergoing complete (CC-0) or near-complete (CC-1) cytoreduction, including at least one colonic resection, and HIPEC. Mean age of patients was 58.8years and CC-0 was possible in 72.4%. Rates of in-hospital mortality and major morbidity were 2.6% and 15.7%. Only 122 (80.3%) patients completed Adjuvant Systemic Chemotherapy (ASCH). Rates of metastatic Total Lymph Nodes (TLN), Para-Aortic and Pelvic Lymph Nodes (PAPLN) and Large Bowel Lymph Nodes (LBLN) were 58.7%, 58.5%, and 51.3%, respectively. Median, 5- and 10-year survival rates were 39months, 43%, and 36.2%, respectively. The recurrence rate was 35.5%. On univariate analysis, CC-1, high Peritoneal Cancer Index (PCI), in-hospital morbidity, and no adjuvant chemotherapy were adverse factors for survival and recurrence. On multivariate analysis, negative survival indicators were the advanced age of patients, extensive peritoneal dissemination, low total number of TLN and no systemic PAPLN. Metastatic LBLN and segmental resection of the small bowel (SIR) were associated with a high risk for recurrence. CC-O is feasible in most advanced ovarian cancer patients and HIPEC may confer a survival benefit. Radical bowel resection, with its entire mesocolon, may be necessary, as its lymph nodes often harbor metastases influencing disease recurrence and survival. The role of metastatic bowel lymph nodes has to be taken into account when assessing the impact of systemic lymphadenectomy in this group of patients.

Factors Associated With Recurrence Of Epithelial Ovarian Cancer In RSUP Dr. Kariadi Semarang

Introductions: Epithelial ovarian cancer accounts for 90% of all ovarian malignancies. More than 70% of patients will experience a relapse even after receiving operative therapy and chemotherapy. There are several prognostic factors that influence the recurrence of ovarian cancer. In Indonesia, especially at Dr. Kariadi Hospital, Semarang, the data as mentioned above is still very limited.objective: Knowing the disease-free survival rate, optimizing surgery and factors related to the incidence of recurrence in epithelial ovarian cancer patients at Dr. Kariadi Hospital SemarangMethods: This study is a retrospective cohort study with survival analysis. Data were collected through medical records, with the study population are patients with a diagnosis of epithelial ovarian cancer who were treated at Dr. Kariadi Hospital Semarang in period January 2018-December 2019. Furthermore, patients who had been remission were observed for signs of disease recurrence for 2 years period.Results: There were 361 patients with epithelial ovarian cancer who underwent primary treatment at Dr. Kariadi Hospital, Semarang in 2018-2019. Furthermore, there were observations of recurrence in 148 patients who achieved remission. Of these 76 patients (51.4%) experienced recurrence, while 72 patients not relapse. From 148 epithelial ovarian cancer patients who underwent cytoreduction surgery at Dr. Kariadi Hospital, Semarang, 113 patients (76.4%) achieved optimal operation with a residu less than 2 cm, while 35 patients (23.6%) were not optimal with a residu more than 2 cm. FIGO stage (HR 2.44) and tumor residu (HR 2.15) were shown to be significant factors associated with the recurrence of epithelial ovarian cancer.Conclusion: Overall disease-free survival in epithelial ovarian cancer at Dr. Kariadi Semarang were 74.8% (6 months), 57.1% (1 year), 42.5% (18 months), and 37.4% (2 years). Tumor residual factors and FIGO stage were shown to be significant prognostic factors influencing the recurrence of epithelial ovarian cancer.

Pancancer analysis of SKA1 mutation and its association with the diagnosis and prognosis of human cancers

This study aims to explore the role of SKA1 in cancer diagnosis and prognosis and to investigate the mechanism by which SKA1 affects the malignant behaviors of ovarian cancer. Herein, we analyzed the oncogenic role of SKA1 at pan-cancer level by multiple informatics databases and verified the analysis by in vitro experiments. As a result, SKA1 was upregulated across cancers and was related to poor clinical outcome and immune infiltration. Specifically, the constructed nomogram showed superior performance in predicting the prognosis of epithelial ovarian cancer patients. Furthermore, the in vitro experiments revealed that silencing SKA1 significantly inhibited the proliferation, migratory ability and enhanced the cisplatin sensitivity of ovarian cancer cells. Therefore, we explored the oncogenic and potential therapeutic role of SKA1 across cancers through multiple bioinformatic analysis and revealed that SKA1 may promote ovarian cancer progression and chemoresistance to cisplatin by activating the AKT-FOXO3a signaling pathway.

Predicting incomplete cytoreduction in patients with advanced ovarian cancer.

The most important prognostic factor for survival in ovarian cancer patients is complete cytoreduction. The preoperative prediction of suboptimal cytoreduction, considered as any residual disease at the end of surgery, could prevent futile surgery and morbidity. Here, we aimed to identify markers in the preoperative abdominal CT scans of an unselected cohort of patients with ovarian cancer that are predictive of incomplete cytoreduction. This is a single-institution retrospective analysis of 105 epithelial ovarian cancer (EOC) patients treated with surgical cytoreduction between 2010 and 2020. Twenty-two variables on preoperative abdominal CT scans were compared to the intraoperative macroscopic findings by Fisher's exact test. Parameters with a significant correlation between intraoperative findings and imaging were analyzed by multivariate binary logistic regression analysis regarding the surgical outcome of complete versus incomplete cytoreduction. Complete cytoreduction (CC), indicated by the absence of macroscopic residual disease, was achieved in 79 (75.2%) of 105 patients and 46 (63.9%) of 72 International Federation of Gynecology and Obstetrics (FIGO) stage III and IV patients. Twenty patients (19%) were incompletely cytoreduced due to miliary carcinomatosis of the small bowel, and six patients (5.7%) had various locations of residual disease. Thirteen variables showed a significant correlation between imaging and surgical findings. Large-volume ascites, absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon in FIGO stage III and IV patients decreased the rate of CC to 26.7% in the multivariate analysis. Large-volume ascites, the absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon are markers in preoperative CT scans predicting a low chance for complete cytoreduction in unselected ovarian cancer patients in a real-world setting.

Plasma exosomal miR-320d, miR-4479, and miR-6763-5p as diagnostic biomarkers in epithelial ovarian cancer.

Exosomal miRNA had been proved as the promising biomarkers for multiple cancers including epithelial ovarian cancer (EOC). This study aimed to validate the diagnostic accuracy of exosomal miR-320d, miR-4479, and miR-6763-5p for EOC. Exosomes isolated from the plasma by ultracentrifugation were verified using TEM, qNano and western blot. MiRNAs sequencing was used to screen out the differential exosomal miRNAs and miR-320d, miR-4479, and miR-6763-5p were selected as candidates, which were further verified by RT-qPCR in 168 healthy donors and 161 primary EOC patients. Besides, the diagnostic accuracy of these three exosomal miRNAs were evaluated using the receiver operating characteristic curve (ROC). MiRNAs sequencing revealed 95 differential exosomal miRNAs between EOC patients and healthy donors. Subsequently, exosomal miR-320d, miR-4479, and miR-6763-5p were significantly down regulated in EOC patients compared with healthy controls and benign patients. More importantly, these three miRNAs could serve as circulating diagnostics biomarkers for EOC, possessing areas under the curve (AUC) of 0.6549, 0.7781, and 0.6834, respectively. Moreover, these three exosomal miRNAs levels were closely associated with lymph node metastasis, meanwhile exosomal miR-320d and miR-4479 expression was related to tumor stage. Exosomal miR-320d, miR-4479, and miR-6763-5p might serve as potential biomarkers for EOC.

Immune Profile of Blood, Tissue and Peritoneal Fluid: A Comparative Study in High Grade Serous Epithelial Ovarian Cancer Patients at Interval Debulking Surgery.

High-grade serous epithelial ovarian carcinoma (HGSOC) is an immunogenic tumor with a unique tumor microenvironment (TME) that extends to the peritoneal cavity. The immunosuppressive nature of TME imposes the major challenge to develop effective treatment options for HGSOC. Interaction of immune cells in TME is an important factor. Hence, a better understanding of immune profile of TME may be required for exploring alternative treatment options. Immune profiling of peritoneal fluid (PF), tumor specimens, and blood were carried out using flowcytometry, ELISA, and Procartaplex immunoassay. The frequency of CD56BrightNK cells and expression of functional receptors were reduced in PF. Increased activating NKp46+CD56DimNK cells may indicate differential antitumor response in PF. Functional receptors on NK, NKT-like and T cells were reduced more drastically in tumor specimens. Soluble ligands MIC-B and PVR were reduced, whereas B7-H6 was increased in PF. Dissemination of tumor cells contributes to soluble ligands in PF. A differential cytokine profile was found in serum and PF as IL-2, IL-8, IL-15, IL-27, IFN-γ, and GM-CSF were elevated specifically in PF. In conclusion, the differential immune profile and correlation of soluble parameters and NK cell receptors with chemo response score may add knowledge to understand anti-tumor immune response to develop effective treatment modality.

Facility level variation in the utilization of neoadjuvant chemotherapy is associated with higher surgical morbidity for patients with advanced stage epithelial ovarian carcinoma

ObjectiveInvestigate outcomes for advanced stage epithelial ovarian cancer (EOC) patients based on facility-level utilization of neoadjuvant chemotherapy (NACT). MethodsStage III-IV EOC patients diagnosed between 2010 and 2016 were identified in the National Cancer Database. Percentage of patients managed with NACT was calculated for facilities, reporting ≥120 patients. Facilities with lowest and highest quartile of NACT rate comprised the low and high-utilizing groups. Clinico-pathological characteristics were collected, and appropriate statistical analysis performed. ResultsHigh- and low-utilizing facilities managed on average 54.1% and 25.4% of patients with NACT respectively. Patients managed at high-utilizing facilities were significantly more likely to be >65 (p = 0.029), have stage IV disease (p < 0.001) and comorbidities (p < 0.001). Patients managed with primary debulking surgery (PDS) at low-utilizing facilities were significantly more likely to be >65, have stage IV disease, and have comorbidities (all, p < 0.001). Patients undergoing PDS at low-utilizing facilities were significantly less likely to achieve complete gross resection (p < 0.001), and were significantly more likely to experience 90-day mortality (p < 0.001), and unplanned 30-day readmission (p < 0.001). After controlling for age, comorbidities, race, insurance status, stage, grade and histology, high-utilizing facilities trended towards better overall survival (OS) (HR: 0.92, 95% CI: 0.85–0.99). Overall, patients undergoing PDS had better OS compared to those who had NACT (median 42 vs 27 months, p < 0.001). ConclusionsDespite treating an EOC population with more advanced disease and comorbidities, high-utilizing facilities have lower surgical morbidity and mortality with no detrimental impact on long-term survival. Careful patient selection to minimize the morbidity and mortality associated with PDS is pivotal.

Single-Cell Sequencing of Malignant Ascites Reveals Transcriptomic Remodeling of the Tumor Microenvironment during the Progression of Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the main cause of mortality among gynecological malignancies worldwide. Although patients with EOC undergo aggregate treatment, the prognosis is often poor. Peritoneal malignant ascites is a distinguishable clinical feature in EOC patients and plays a pivotal role in tumor progression and recurrence. The mechanisms of the tumor microenvironment (TME) in ascites in the regulation of tumor progression need to be explored. We comprehensively analyzed the transcriptomes of 4680 single cells from five EOC patients (three diagnostic samples and two recurrent samples) derived from Gene Expression Omnibus (GEO) databases. Batch effects between different samples were removed using an unsupervised deep embedding single-cell cluster algorithm. Subcluster analysis identified the different phenotypes of cells. The transition of a malignant cell state was confirmed using pseudotime analysis. The landscape of TME in malignant ascites was profiled during EOC progression. The transformation of epithelial cancer cells into mesenchymal cells was observed to lead to the emergence of related anti-chemotherapy and immune escape phenotypes. We found the activation of multiple biological pathways with the transition of tumor-associated macrophages and fibroblasts, and we identified the infiltration of CD4+CD25+ T regulatory cells in recurrent samples. The cell adhesion molecules mediated by integrin might be associated with the formation of the tumorsphere. Our study provides novel insights into the remodeling of the TME heterogeneity in malignant ascites during EOC progression, which provides evidence for identifying novel therapeutic targets and promotes the development of ovarian cancer treatment.

Clinical Significance of Methyltransferase-like 16 Expression in Epithelial Ovarian Cancer.

To detect methyltransferase-like (METTL) 16 expression in epithelial ovarian cancer (EOC) by immunohistochemistry (IHC), and its relationship with clinicohistopathological parameters and prognosis. Observational study. Department of Gynaecology and Pathology, The First Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), from February to June 2022. METTL16 expression in 115 EOC patients was evaluated by IHC. According to the immunoreactive score (IRS), scores <6 represented low expressions and ≥6 high expressions. Clinicopathologic data and follow-up information were collected for statistical evaluation. METTL16 expression decreased in EOC (p = 0.001) and affected the poor prognosis of EOC patients. Low METTL16 patients expression had significantly higher frequencies of advanced FIGO stage, low grade, more lymph node metastasis, high CA125 levels, bilateral disease, distant metastasis, and high frequency of neural/vascular invasion compared to high METTL16 patients (p ≤0.001, <0.001, <0.001, 0.017, 0.027, <0.001, and 0.010, respectively). The survival analysis showed that the overall survival (p <0.0001) as well as the disease-free survival (p <0.0001) were remarkably shorter in low METTL16 patients compared to high METTL16 patients, suggesting worse survival. There was a clear association between the expression of METTL16, poor prognostic factors, and lower survival of EOC patients, suggesting that it might exert a vital effect on the malignant progression / prognosis of EOC. Epithelial ovarian cancer (EOC), METTL16, Immunohistochemistry, Prognosis.