Stage Epithelial Ovarian Cancer Research Articles

Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

Contrast-enhanced CT radiomics for preoperative prediction of stage in epithelial ovarian cancer: a multicenter study

BackgroundPreoperative prediction of International Federation of Gynecology and Obstetrics (FIGO) stage in patients with epithelial ovarian cancer (EOC) is crucial for determining appropriate treatment strategy. This study aimed to explore the value of contrast-enhanced CT (CECT) radiomics in predicting preoperative FIGO staging of EOC, and to validate the stability of the model through an independent external dataset.MethodsA total of 201 EOC patients from three centers, divided into a training cohort (n = 106), internal (n = 46) and external (n = 49) validation cohorts. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening radiomics features. Five machine learning algorithms, namely logistic regression, support vector machine, random forest, light gradient boosting machine (LightGBM), and decision tree, were utilized in developing the radiomics model. The optimal performing algorithm was selected to establish the radiomics model, clinical model, and the combined model. The diagnostic performances of the models were evaluated through receiver operating characteristic analysis, and the comparison of the area under curves (AUCs) were conducted using the Delong test or F-test.ResultsSeven optimal radiomics features were retained by the LASSO algorithm. The five radiomics models demonstrate that the LightGBM model exhibits notable prediction efficiency and robustness, as evidenced by AUCs of 0.83 in the training cohort, 0.80 in the internal validation cohort, and 0.68 in the external validation cohort. The multivariate logistic regression analysis indicated that carcinoma antigen 125 and tumor location were identified as independent predictors for the FIGO staging of EOC. The combined model exhibited best diagnostic efficiency, with AUCs of 0.95 in the training cohort, 0.83 in the internal validation cohort, and 0.79 in the external validation cohort. The F-test indicated that the combined model exhibited a significantly superior AUC value compared to the radiomics model in the training cohort (P < 0.001).ConclusionsThe combined model integrating clinical characteristics and radiomics features shows potential as a non-invasive adjunctive diagnostic modality for preoperative evaluation of the FIGO staging status of EOC, thereby facilitating clinical decision-making and enhancing patient outcomes.

Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients.

Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.

Comparison of platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios with epithelial ovarian cancer stages

Objectives: Epithelial ovarian cancer (EOC) is the most common histologic type among ovarian cancers. It is usually diagnosed at an advanced stage and the prognosis worsens. The aim of our study was to investigate the predictive value of serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), which are systemic inflammatory response markers in EOC stages. Methods: In this study, 140 patients diagnosed with primary EOC in İzmir Katip Çelebi University Atatürk Training and Research Hospital Gynecology and Obstetrics Clinic between 01.01.2012-01.07.2019 were included. The cases were staged using the FIGO 2014 Ovarian Cancer Staging system. Whether the PLR and NLR values were different between the stages were analyzed with appropriate statistical analysis methods. Results: A total of 140 patients, 54 were in the early stage (Stage I: 47; Stage II: 7) and 86 were in the advanced stage (Stage III: 73; Stage IV: 13). The PLR and NLR values differed between the four stages (p = 0.003 and p = 0.032, respectively). The PLR value was different between the early and advanced stages (p = 0.033), the AUC value was 0.607, the optimum cut-off was 220, the sensitivity was 47%, and the specificity was 81% in the early and advanced stage discrimination. Accordingly, the Odds ratio of PLR for advanced EOC was 3.82 (95% CI: 1.70-8.57, p = 0.0011). Conclusions: The NLR and PLR values were found to have a prognostic value in the discrimination of EOC stages. It has been determined that PLR value may play a predictive role in advanced EOC before surgery.

The Role of Interleukin 6 (IL6), Cancer Antigen-125 (CA-125), and Human Epididymis Protein 4 (HE4) to predict tumor resectability in the advanced epithelial ovarian cancer patients.

A study of tumor resectability in pre-operative patients with advanced epithelial ovarian cancer is required to predict primary surgical benefits accurately. This study aims to investigate IL6, CA-125 and HE4 to predict tumor resectability in the pre-operative patients with advanced epithelial ovarian cancer. This cross-sectional study was conducted in the polyclinic, oncology and gynecology inpatient room of Dr. M. Jamil Padang Hospital from June until December 2022. Advanced epithelial ovarian cancer stage based on histology result from FIGO stages IIIB-IVA. IL6, CA-125, and HE4 were measured using ECLIA (electrochemiluminescence immunoassay). Categorical data were assessed using Chi-square and Mann-Whitney tests. Numerical variable correlations were analyzed using Pearson Correlation tests. While the correlation between numerical and nominal variables was analyzed using the Eta correlation test. A p-value of <0,05 was considered a significant correlation. The cut-off value of serum IL6, CA-125, and HE4 was determined with a ROC curve. The sensitivity and specificity of each clinical parameter were calculated. There was a significant difference in IL-6 (1328 vs 752 pg/ml; p<0,001), CA-125 (1260,5 vs 819,5 U/ml; p<0,001), and HE4 levels (1320 vs 760 pmol/L; p<0,001) between patients with tumor resectability of > 1 cm (suboptimal) vs < 1 cm (optimal). There was a correlation between IL6 (r = 0,832), CA-125 (r = 0,716), and HE4 (r = 0,716) with tumor resectability. Measuring IL6, CA-125, and HE4 levels is useful for clinicians to predict tumor resectability in pre-operative patients with advanced epithelial ovarian cancer.

Electrolyte imbalance causes suppression of NK and T cell effector function in malignant ascites

BackgroundMalignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis. Due to its complex composition of cellular and acellular components malignant ascites creates a unique tumor microenvironment, which mediates immunosuppression and promotes progression of disease. However, the immunosuppressive mechanisms remain poorly understood.MethodsIn the present study, we explored the antitumor activity of healthy donor NK and T cells directed against ovarian cancer cells in presence of malignant ascites derived from patients with advanced or recurrent peritoneal carcinomatosis. A wide range of methods was used to study the effect of ascites on NK and T cells (FACS, ELISA, EliSpot, qPCR, Live-cell and confocal microscopy, Western blot and electrolyte flux assays). The ascites components were assessed using quantitative analysis (nephelometry, potentiometry and clinical chemistry) and separation methods (dialysis, ultracentrifugal filtration and lipid depletion).ResultsAscites rapidly inhibited NK cell degranulation, tumor lysis, cytokine secretion and calcium signaling. Similarly, target independent NK and T cell activation was impaired in ascites environment. We identified imbalanced electrolytes in ascites as crucial factors causing extensive immunosuppression of NK and T cells. Specifically, high sodium, low chloride and low potassium content significantly suppressed NK-mediated cytotoxicity. Electrolyte imbalance led to changes in transcription and protein expression of electrolyte channels and impaired NK and T cell activation. Selected inhibitors of sodium electrolyte channels restored intracellular calcium flux, conjugation, degranulation and transcript expression of signaling molecules. The levels of ascites-mediated immunosuppression and sodium/chloride/potassium imbalance correlated with poor patient outcome and selected molecular alterations were confirmed in immune cells from ovarian cancer patients.ConclusionOur data suggest a novel electrolyte-based mechanism of immunosuppression in malignant ascites of patients with peritoneal carcinomatosis. We show for the first time that the immunosuppression of NK cytotoxicity in coculture assays is correlated to patient poor survival. Therapeutic application of sodium channel inhibitors may provide new means for restoring immune cell activity in ascites or similar electrolyte imbalanced environments.

Minimally Invasive Staging of Early-Stage Epithelial Ovarian Cancer versus Open Surgery in Terms of Feasibility and Safety: A Systematic Review and Meta-Analysis.

Epithelial ovarian cancer is women's fourth most common oncological cause of death. One of the main prognostic factors in ovarian cancer is the tumor stage. For instance, surgical staging of the disease is focal when choosing the best therapeutic option for each case. Although open surgery is the prevalent approach for staging and treating ovarian cancer, the use of minimally invasive surgery (MIS) has found recent application in staging or restaging cases of early disease. Our work compares oncological outcomes after MIS staging for FIGO I epithelial ovarian cancer with the laparotomic approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations, we systematically searched the Pub Med and Scopus databases in February 2023. No temporal nor geographical limitation was made. We included the articles containing data about Disease-Free Survival (DFS) and Overall Survival (OS), Recurrence Rates (RR), and Upstaging Rates (UpR). We used comparative studies for the meta-analysis. After the database search and article selection, 19 works matched the inclusion criteria for the systematic review. Eleven of these were comparative studies between MIS and Open Surgical Staging (OSS) approaches for ovarian cancer staging and were included in the meta-analysis. The meta-analysis did not show a statistically significant difference between the MIS and the OSS group concerning DFS, OS, and RR. Only Upstaging Rate ≥ FIGO Stage II was statistically significative higher in the OSS group. Likewise, MIS is confirmed to be an approach with a lower profile of surgical complications. In conclusion, our study did not show one approach to be safer than the other. However, the lack of dedicated studies limits the evidence of our study. For instance, we recommend adequately selecting the specimen, minimizing the risk of spillage, and optimizing surgical staging.

Trends in ovarian cancer incidence and incidence-based mortality: A 15-year population-based analysis.

5570 Background: The predicted incidence and incidence-based mortality (IBM) of ovarian cancer (OC) in 2023 is lower than prior years. OC encompasses a range of heterogeneous cancers with subtypes categorized on histology and site of origin. Given differences in survival and treatment paradigms, we aim to characterize trends in OC incidence and IBM based on histology and site of origin to determine what factors are responsible for the decline. Methods: Patients with OC from 2000-2019 were identified from the US Surveillance, Epidemiology, and End Results 17 registry database. Using ICD-O-3 codes, patients with epithelial, stromal, and germ cell cancers of the ovary, fallopian tube, and peritoneum were included. Incidence and IBM were reported as age-adjusted rates and stratified by cancer subtype. Using Joinpoint 4.9.1.0, we characterized piecewise log-linear time trends to identify inflection points in the rates’ annual percentage change (APC). Results: The incidence of epithelial OC decreased significantly from 2004-2019 (APC -1.24%). When stratified by disease stage, this trend was seen in distant disease (APC -2.11%) and unknown/unstaged disease (APC -3.40%); however, there was a significant increase in incidence of local disease (APC +0.83%). There was no significant change in the incidence of germ cell and stromal OC from 2004-2019 in all stages. (APC -0.30% and +0.33%). Among all OC subtypes, there was a significant decline in incidence from 2000-2019 (APC -1.57%) with a sharper decline from 2015-2019 (APC -3.41%). Among all cancer subtypes, the incidence trended down from 2000-2019, with a significant decline from 2015-2019 (APC -2.37%). Similar trends are observed in IBM. Among all stages of epithelial OC, there was a significant decrease in IBM from 2006-2019 (APC -2.02%). When stratified by disease stage, there was a decline in IBM in local disease (APC -7.19%, 2014-2019) and distant disease (APC -2.44%, 2010-2019). There were no changes in IBM of germ cell and stromal OC from 2004-2019 (APC +0.78% and -0.20%). Among all cancers, IBM significantly decreased from 2006-2019 (APC -2.28%). When stratified by disease stage, there was no change among local disease and an increase in regional disease from 2006-2019 with the increase from 2006-2010 (APC +14.35%) compared to 2010-2019 (APC +1.45%). Conversely, there was a significant decrease in IBM for distant disease (APC -2.51% from 2010-2019) and unknown/unstaged disease (APC -3.27% from 2006-2019). Conclusions: There has been an overall decline in incidence and IBM of OC over a 15-year period, primarily driven by the epithelial histology. Over the past 20 years, OC has been increasingly diagnosed at earlier stages with a corresponding improvement in survival. While stage migration and improved survival may contribute to these trends, they do not entirely explain them. As new treatments become available, the incidence and IBM of OC may further decline.

Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage ovarian cancer: A prospective multicentre study (SELLY).

e17579 Background: Comprehensive surgical staging of early epithelial ovarian cancer includes systematic paraaortic and bilateral pelvic lymphadenectomy but its therapeutic role is controversial and it is associated with potential severe morbidity. The feasibility of sentinel lymph-node (SLN) identification in early stage ovarian cancer has been shown only. We did a prospective multicenter study to assess the feasibility, detection rate and diagnostic accuracy of the SLN procedure in predicting the pathological pelvic-node status in patients with early stage ovarian cancer. Methods: This is a phase II single arm study (EUDRACT 2019-001088-58) including patients with presumed stage I-II epithelial ovarian cancer planned for immediate or delayed minimally-invasive comprehensive staging. The ovarian pedicle is injected with 2 mL of a 1.25 mg/mL indocyanine green (ICG) solution. The pelvic and lumbo-aortic retroperitoneum is then accessed and inspected to identify and remove SLNs. Staging is then completed including systematic pelvic and para-aortic lymphadenectomy and an histopathological examination of all nodes is performed. The primary endpoint was estimation of the sensitivity and sensibility of SLN in predicting nodal status. Assuming a sensitivity of 98.5% in predicting positive sentinel lymph nodes at histology, a pathological lymph node prevalence of 14.2%, a precision of estimate (i.e. the maximum marginal error) d=5%, a type I error α = 0.05, a sample size of 141 patients is needed to test the general hypothesis (i.e. to answer whether SLN(s) identified with ICG can accurately predict nodal status at histology of patients with apparently early EOC). Assuming a drop-out rate of 20%, a total of 176 patients will be enrolled in the study. Results: One-hundred and seventy-six patients were included with a drop-out rate of 22%. Sentinel node was identified in 102 patients (detection rate, 58%, [95% CI: 51-65]). There were no clinical differences between patients with successful or unsuccessful mapping. Both the infundibolopelvic ligament and the legamentum ovarii proprium were injected in 29.0% of cases. Twenty-one patients had positive nodes and 71% of them showed successful mapping. Among the latter, a negative sentinel node was identified in 3 patients (Sensitivity 78.6% [95% CI: 57-100]; Specificity 100%; Accuracy 97% [95% CI: 94-100]; PPV 100%; NPV 96,6% [95% CI: 93-100]). Twenty-two (12.5%) intra- and 25 (14.2%) postoperative complications occurred (12 G1; 9 G2; 2 G3, 2 G4). Clinical trial information: EUCTR2019-001088-58 .

Overexpression of CLDN16 in ovarian cancer is modulated by PI3K and PKC pathways

Epithelial ovarian cancer (EOC) is the gynecological malignant tumor of poorest prognosis and higher mortality rate. Chemotherapy is the base of high-grade serous ovarian cancer (HGSOC) treatment; however, it favors the emergence of chemoresistance and metastasis. Thus, there is an urge to search for new therapeutic targets, such as proteins related to cellular proliferation and invasion. Herein, we investigated the expression profile of claudin-16 (CLDN16 protein and CLDN16 transcript) and its possible functions in EOC. In silico analysis of CLDN16 expression profile was performed using data extracted from GENT2 and GEPIA2 platforms. A retrospective study was carried out with 55 patients to evaluate the expression of CLDN16. The samples were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, molecular docking, sequencing, and immunoblotting assays. Statistical analyzes were performed using Kaplan-Meier curves, one-way ANOVA, Turkey posttest. Data were analyzed using GraphPad Prism 8.0. In silico experiments showed that CLDN16 is overexpressed in EOC. 80.0% of all EOC types overexpressed CLDN16, of which in 87% of the cases the protein is restricted to cellular cytoplasm. CLDN16 expression was not related to tumor stage, tumor cells differentiation status, tumor responsiveness to cisplatin, or patients' survival rate. When compared to data obtained from in silico analysis regarding EOC stage and degree of differentiation, differences were found in the former but not in the later, neither in survival curves. CLDN16 expression in HGSOC OVCAR-3 cells increased by 1.95-fold (p < 0.001), 2.32-fold (p < 0.001), and 6.57-fold (p < 0.001) via PKC, PI3K, and estrogen pathways, respectively. Altogether, our results suggest that despite the low number of samples included in our in vitro studies, adding to the expression profile findings, we provided a comprehensive study of CLDN16 expression in EOC. Therefore, we hypothesize that CLDN16 is a potential target in the diagnosis and treatment of the disease.

Survival in stage IV ovarian cancer with increased use of debulking surgery and bevacizumab

ObjectivesAdvanced ovarian cancer has a poor prognosis, with a 5 year survival probability of <30%. Attempts to improve survival have focused on debulking surgery and systemic therapy. We assessed the...

Prognostic Outcome of Mesenchymal Transition Biomarkers in Correlation with EGFR Expression in Epithelial Ovarian Carcinoma Patients

CD44 is an epithelial-mesenchymal transition (EMT) surface receptor that regulates the interactivity between the cells and the extracellular matrix, thereby promoting cell migration. The epidermal growth factor receptor (EGFR) family is a trans-membrane kinase-related protein. It regulates cell adhesion proteins, which may promote cell proliferation and invasiveness. Mesenchymal epithelial transition (MET) is another EMT receptor that stimulates cell proliferation, invasion, survival, and angiogenesis. This study aimed to evaluate the prognostic impact of CD44, EGFR expressions, and MET gene amplification in epithelial ovarian cancer (EOC). This is a retrospective cohort study, including 85 cases of EOC. CD44 and EGFR expressions were evaluated in both epithelial and stromal cells by immunohistochemistry. Tumor cells also underwent a cytogenetic analysis using fluorescent in situ hybridization (FISH) to detect MET gene amplification. High CD44 expression in tumors was significantly associated with serous subtypes (P=0.001), peritoneal deposits (P=0.002), and advanced stage (P=0.002). EGFR high tumor expression demonstrated a significant association with lymph node metastasis (P=0.038) and the advanced stage of EOC (P=0.016). Increased copy number of the MET gene was significantly associated with partial therapy response (P=0.030). CD44 and EGFR tumor high expression was associated with poor overall survival (OS). In addition, MET gene gain in tumors was associated with a shorter OS (P=0.000). EMT biomarkers (CD44 and MET) and EGFR expression in EOC are independent prognostic factors for OS. MET gene increase copy number was detected in cases of serous neoplasm and associated with poor survival and minimal therapy response.

Clinical Significance of Tie-2-Expressing Monocytes/Macrophages and Angiopoietins in the Progression of Ovarian Cancer—State-of-the-Art

Tumour growth and metastasis are specific to advanced stages of epithelial ovarian cancer (EOC). Tumour angiogenesis is an essential part of these processes. It is responsible for providing tumours with nutrients, metabolites, and cytokines and facilitates tumour and immune cell relocation. Destabilised vasculature, a distinctive feature of tumours, is also responsible for compromising drug delivery into the bulk. Angiogenesis is a complex process that largely depends on how the tumour microenvironment (TME) is composed and how a specific organ is formed. There are contrary reports on whether Tie-2-expressing monocytes/macrophages (TEMs) reported as the proangiogenic population of monocytes have any impact on tumour development. The aim of this paper is to summarise knowledge about ovarian-cancer-specific angiogenesis and the unique role of Tie-2-expressing monocytes/macrophages in this process. The significance of this cell subpopulation for the pathophysiology of EOC remains to be investigated.

Neoadjuvant Chemotherapy Versus Primary Debulking Surgery in FIGO Stage III and IV Epithelial Ovarian, Tubal or Peritoneal Cancer: A Systematic Review and Meta-Analysis.

Objective: To investigate whether neoadjuvant chemotherapy (NACT) confers superior outcomes compared to primary debulking surgery (PDS) in patients with stage III and IV epithelial ovarian, tubal or peritoneal cancer as well as in patients with high tumour load. Methods: We searched the electronic databases PubMed, Cochrane Central Register of Controlled trials, and Scopus from inception to March 2021. We considered randomised controlled trials (RCTs) comparing NACT with PDS for women with epithelial ovarian cancer (EOC) stages III and IV. The primary outcomes were overall survival and progression-free survival. Secondary outcomes were optimal cytoreduction rates, peri-operative adverse events, and quality of life. Results: Six RCTs with a total of 1901 participants were included. Meta-analysis demonstrated similar overall survival (HR = 0.96, 95% CI [0.86-1.07]) and progression-free survival (HR = 0.98, 95% CI [0.89-1.08]) between NACT and PDS. Subgroup analyses did not demonstrate higher survival for stage IV patients (HR = 0.88, 95% CI [0.71-1.09]) nor for patients with metastatic lesions >5cm (HR = 0.86, 95% CI [0.69-1.08]) treated with NACT, albeit with some uncertainty due to imprecision. Similarly, no survival benefit was observed in the subgroup of patients with metastatic lesions >10cm (HR = 0.94, 95% CI [0.78-1.12]). NACT was associated with significantly higher rates of complete cytoreduction (RR = 2.34, 95% CI [1.48-3.71]). Severe peri-operative adverse events were less frequent in the NACT arm (RR = 0.34, 95% CI [0.16-0.72]. Conclusion: Patients with stage III and IV epithelial ovarian cancer undergoing NACT or PDS have similar overall survival. NACT is likely associated with higher rates of complete cytoreduction and lower risk of severe adverse events and peri-operative death.

Changes in subcellular localization of Lysyl-tRNA synthetase and the 67-kDa laminin receptor in epithelial ovarian cancer metastases.

Although lysyl-tRNA synthetase (KARS1) is predominantly located in the cytosol, it is also present in the plasma membrane where it stabilizes the 67-kDa laminin receptor (67LR). This physical interaction is strongly increased under metastatic conditions. However, the dynamic interaction of these two proteins and the turnover of KARS1 in the plasma membrane has not previously been investigated. Our objective in this study was to identify the membranous location of KARS1 and 67LR and investigate if this changes with the developmental stage of epithelial ovarian cancer (EOC) and treatment with the inhibitor BC-K01. In addition, we evaluated the therapeutic efficacy of BC-K01 in combination with paclitaxel, as the latter is frequently used to treat patients with EOC. Overall survival and prognostic significance were determined in EOC patients according to KARS1 and 67LR expression levels as determined by immunohistochemistry. Changes in the location and expression of KARS1 and 67LR were investigated in vitro after BC-K01 treatment. The effects of this compound on tumor growth and apoptosis were evaluated both in vitro and in vivo. EOC patients with high KARS1 and high 67LR expression had lower progression-free survival rates than those with low expression levels of these two markers. BC-K01 reduced cell viability and increased apoptosis in combination with paclitaxel in EOC cell xenograft mouse models. BC-K01 decreased membranous KARS1 expression, causing a reduction in 67LR membrane expression in EOC cell lines. BC-K01 significantly decreased in vivo tumor weight and number of nodules, especially when used in combination with paclitaxel. Co-localization of KARS1 and 67LR in the plasma membrane contributes to EOC progression. Inhibition of the KARS1-67LR interaction by BC-K01 suppresses metastasis in EOC.

Systematic Pelvic and Para-Aortic Lymphadenectomy During Fertility-Sparing Surgery in Patients With Early-Stage Epithelial Ovarian Cancer: A Retrospective Study.

ObjectiveThe implication of pelvic and para-aortic lymphadenectomy in surgical staging of early-stage epithelial ovarian cancer (eEOC) is still debated. Limited data are available about systematic lymphadenectomy during fertility-sparing surgery (FSS) in patients with eEOC.MethodsThe medical records of 38 patients with FIGO stage I EOC and below 40 years who underwent FSS at our hospital between January 2003 and December 2018 were retrospectively reviewed.ResultsAmong them, 18 patients (47.4%) underwent comprehensive lymphadenectomy, 11 patients (28.9%) underwent lymph node sampling, and 9 patients (23.7%) did not undergo lymphadenectomy. There was no statically significant difference in age, histology, grade, surgical approach, chemotherapy, and gestation among the three groups. With a median follow-up of 52.5 months (range: 24–153), three patients (7.9%) with FIGO stage IC EOC developed tumor recurrence. In these patients, progress-free survival (PFS) was 92.1%, and overall survival (OS) was 94.7%. No significant difference in the OS. Three patients had among all the patients, 15 patients (39.5%) had gestation after treatment, and 23 patients (60.5%) did not have gestation after treatment.ConclusionThe number of lymph nodes removed did not significantly affect survival eEOC with FSS. Systematic pelvic and para-aortic lymphadenectomy could not be performed for mucious eEOC patients with FSS if intraoperative freezing in confirmed and no suspicious lymph nodes are found. A better understanding of sentinel lymph node biopsy may help to identify whether the patient requires FSS.

Correlation of Preoperative Level of Serum Ca125 with Surgical Staging of Ovarian Cancer

Background: Ovarian cancer is one of the leading cause of mortality and morbidity of gynaecological malignancies. Lack of early demonstration of symptoms and lack of effective screening tests, ovarian tumours are usually diagnosed at an advanced stage. Different studies shows the association of pre-operative serum CA125 level with the surgical staging of ovarian cancer. Objective: To find out the correlation of pre-operative level of serum CA 125 with the surgical staging (FIGO-2014) of ovarian cancer. Methodology: This cross sectional study was carried out among 81 subjects in the department of gynaecological oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from August 2018 to September 2019. Sampling technique was purposive. All consecutive patients admitted at department of gynaecological oncology, BSMMU with diagnosed ovarian cancer were included in this study. Data were collected and documented on a preformed and pretested structured questionnaire. Clinical examinations and relevant investigations were done and recorded accordingly. Result: Mean age of the study subjects was 45.7 ± 15.2 years with a range of 13-75 years. Mean BMI was 23.3 ± 3.0 kg/m2 and mean age of marriage was 16.1 ± 2.8 years. Maximum study subjects had stage III (44.4%) followed by stage II (23.5%), stage I (21.0%) and stage IV (11.1%). Preoperative CA-125 was &gt;35 U/ml in 90.1% cases. Serum CA-125 was elevated at the advanced stage of ovarian cancer. Maximum study subjects had serous tumors (70.4%) followed by mucinous tumors (11.5%), endometrioid adenocarcinoma (7.4%), malignant teratoma (4.9%) and clear cell tumors (3.7%). Serum CA-125 had significant positive correlation with surgical stages of ovarian epithelial cancer. Conclusion: Surgical stage of epithelial ovarian cancer significantly correlates with CA-125. Bangladesh Med Res Counc Bull 2021; 47(2): 110-117

Effect of bevacizumab combined with chemotherapy on SDF-1 and CXCR4 in epithelial ovarian cancer and its prognosis

BackgroundThe effect of bevacizumab combined with chemotherapy on the expression of stromal cell-derived factor-1 (SDF-1) and receptor CXCR4 in epithelial ovarian cancer tumor cells and its prognosis are unknown. Our work aimed to investigate the effect of chemotherapy +/− bevacizumab on these markers and the impact of this treatment modality in clinical outcomes.MethodsAltogether 68 patients with epithelial ovarian cancer who were treated with chemotherapy in our hospital from June 2018 to June 2019 were selected. It was an open-labeled and controlled clinical trial (ethical approval no. 20180435). The patients were grouped according to their admission order. Patients treated with paclitaxel and carboplatin were included in group A, while patients treated with bevacizumab, paclitaxel, and carboplatin were included in group B. qRT-PCR was used to detect the changes of SDF-1 and CXCR4 before and after chemotherapy. Various clinical indicators of patients in the two groups were recorded to analyze the clinical efficacy, and safety of different treatment modalities and the prognosis of the two groups was analyzed.ResultsThe relative expression of SDF-1 and CXCR4 was positively correlated with epithelial ovarian cancer stages (P<0.00). Together, SDF-1 and CXCR4 were positively correlated in epithelial ovarian cancer staging (P<0.001). SDF-1 and CXCR4 in both groups after chemotherapy were significantly decreased (P<0.001), and the downregulation of SDF-1 and CXCR4 expression in group B was significantly higher than that in group A after chemotherapy (P<0.001). No significant difference in the metastasis rates of the two groups before chemotherapy was observed (P>0.05), but the recurrence rate after 1 year was lower in group B than in group A (P<0.05).ConclusionAdding bevacizumab diminished the expression of related cancer markers SDF-1 and CXCR4 more than chemotherapy alone in patients with epithelial ovarian cancer. Furthermore, better rates of recurrence with no concerns regarding adverse drug reactions or quality of life were seen in bevacizumab plus chemotherapy group.

Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

Overall Survival and Related Factors of Advanced-stage Epithelial Ovarian Cancer Patients Underwent Debulking Surgery in Jakarta, Indonesia: A Single-center Experience

AIM: The worrisome prognosis of advanced-stage epithelial ovarian cancer (EOC) needs a new perspective from developing countries. Thus, we attempted to study the 5-year overall survival (OS) of advanced-stage EOC patients who underwent debulking surgery in an Indonesian tertiary hospital. METHODS: A retrospective study recruited forty-eight subjects between 2013 and 2015. We conducted multiple logistic regression analyses to predict risk factors leading to unwanted disease outcomes. The OS was evaluated through the Kaplan–Meier curve and Log-rank test. Cox proportional hazards regression examined prognostic factors of patients. RESULTS: Prominent characteristics of our patients were middle age (mean: 51.9 ± 8.9 years), obese, with normal menarche onset, multiparous, not using contraception, premenopausal, with serous EOC, and FIGO stage IIIC. The subjects mainly underwent primary debulking surgery (66.8%), with 47.9% of all individuals acquiring optimal results, 77.1% of patients treated had the residual disease (RD), and 52.1% got adjuvant chemotherapy. The risk factor for serous EOC was menopause (odds ratio [OR] = 4.82). The predictors of suboptimal surgery were serous EOC (OR = 8.25) and FIGO stage IV (OR = 11.13). The different OS and median survival were observed exclusively in RD, making it an independent prognostic factor (hazard ratio = 3.50). 5-year A five year OS and median survival for patients with advanced-stage EOC who underwent debulking surgery was 37.5% and 32 months, respectively. Optimal versus suboptimal debulking surgery yielded OS 43.5% versus 32% and median survival of 39 versus 29 months. Both optimal and suboptimal debulking surgery followed with chemotherapy demonstrated an OS 40% lower than those not administered (46.2% and 20%, respectively). The highest 5-year OS was in serous EOC (50%). Meanwhile, the most extended median survival was with mucinous EOC (45 months). CONCLUSION: Chemotherapy following optimal and suboptimal debulking surgery has the best OS among approaches researched in this study. RD is a significant prognostic factor among advanced-stage EOC. Suboptimal surgery outcomes can be predicted by stage and histological subtype.