Ovarian Survival Research Articles

Associations of Healthcare Affordability, Availability, and Accessibility with Quality Treatment Metrics in Patients with Ovarian Cancer.

Differential access to quality care is associated with racial disparities in ovarian cancer survival. Few studies have examined the association of multiple healthcare access (HCA) dimensions with racial disparities in quality treatment metrics, that is, primary debulking surgery performed by a gynecologic oncologist and initiation of guideline-recommended systemic therapy. We analyzed data for patients with ovarian cancer diagnosed from 2008 to 2015 in the Surveillance, Epidemiology, and End Results-Medicare database. We defined HCA dimensions as affordability, availability, and accessibility. Modified Poisson regressions with sandwich error estimation were used to estimate the relative risk (RR) for quality treatment. The study cohort was 7% NH-Black, 6% Hispanic, and 87% NH-White. Overall, 29% of patients received surgery and 68% initiated systemic therapy. After adjusting for clinical variables, NH-Black patients were less likely to receive surgery [RR, 0.83; 95% confidence interval (CI), 0.70-0.98]; the observed association was attenuated after adjusting for healthcare affordability, accessibility, and availability (RR, 0.91; 95% CI, 0.77-1.08). Dual enrollment in Medicaid and Medicare compared with Medicare only was associated with lower likelihood of receiving surgery (RR, 0.86; 95% CI, 0.76-0.97) and systemic therapy (RR, 0.94; 95% CI, 0.92-0.97). Receiving treatment at a facility in the highest quartile of ovarian cancer surgical volume was associated with higher likelihood of surgery (RR, 1.12; 95% CI, 1.04-1.21). Racial differences were observed in ovarian cancer treatment quality and were partly explained by multiple HCA dimensions. Strategies to mitigate racial disparities in ovarian cancer treatment quality must focus on multiple HCA dimensions. Additional dimensions, acceptability and accommodation, may also be key to addressing disparities.

Survival Advantage of Lymphadenectomy in Patients with Ovarian Cancer

We investigated the survival effect of lymphadenectomy in ovarian cancer. The five-year progression-free and overall survival in early-stage ovarian cancer were not affected. Preliminary, unadjusted analysis in advanced ovarian cancer suggested an improvement in survival. However, after adjusting for other factors, e.g. ECOG performance status and patients’ age, this survival advantage vanished. Our analysis suggests that systemic pelvic and para-aortic lymphadenectomy was not associated with an improvement of the progression-free and overall survival of patients with optimally debulked ovarian cancer.

Prognostic markers of inflammation in endometrioid and clear cell ovarian cancer

ObjectivesCancer-related systemic inflammation has been associated with prognosis in multiple cancer types. Conversely, local inflammation, which is characterized by dense intratumoral immune infiltrates, is a favorable predictor of survival outcome....

Pre-diagnosis Dietary One-Carbon Metabolism Micronutrients Consumption and Ovarian Cancer Survival: A Prospective Cohort Study.

Background and AimsEpidemiological evidence on the relation between one-carbon metabolism (OCM) micronutrients intake and ovarian cancer (OC) survival are limited and conflicting. We evaluated the aforementioned associations in a prospective cohort-the Ovarian Cancer Follow-Up Study.MethodsA total of 635 newly diagnosed OC patients aged 18–79 y were enrolled in the present study. Dietary intake related to one-carbon metabolism, including methionine, vitamins B2, B3, B6, B9, B12, choline, and betaine, was assessed using a validated 111-item food frequency questionnaire. Deaths were ascertained until March 31, 2021, via medical records and active follow-up. Cox proportional hazards regression model was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for these aforementioned associations.ResultsDuring a median follow-up of 37.2 months (interquartile: 24.7–50.2 months), 114 deaths were identified. We observed an improved survival with the highest compared with the lowest tertile of dietary vitamin B6 (HR = 0.52, 95%CI: 0.32–0.84, P-trend <0.05) and choline intake (HR = 0.50, 95%CI: 0.30–0.83, P-trend <0.05). No significant associations with OC survival were observed for dietary vitamins B2, B3, B9, B12, methionine, and betaine intake. We also observed a curvilinear association between vitamin B6 intake and OC survival (P non-linear <0.05).ConclusionOur study suggests that pre-diagnosis higher intake of vitamin B6 and choline may improve OC survival. Further clarification of these associations is warranted.

CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer—A Multicenter Analysis

Simple SummaryLow-grade serous cancer (LGSC) accounts for approximately 5% of all ovarian cancers. It is characterized by its high resistance to chemotherapy. Cytoreductive surgery, therefore, is the primary treatment modality for this disease and previous studies have shown that complete removal of all visible tumor tissue should be achieved. In this study, 176 women with LGSC were included and most of them had advanced disease stages, where the disease had already spread. CA-125 is a biomarker that has been previously studied in ovarian cancer. We have found that CA-125 level following treatment of LGSC is an important and independent prognostic factor for progression-free and overall survival. It may be a better surrogate for the true amount of residual disease following treatment compared to the gross estimation of visible residual disease during surgery.Objective: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. Methods: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. Results: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96–1.01 and 0.98; 95%CI 0.95–1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43–12.73) and OS (HR 1.69, 95%CI 0.56–5.05). Elevated CA-125 (≥35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (≥35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36–5.81) and OS (HR 6.62, 95%CI 2.45–17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). Conclusion: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. Highlights: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.

Germline BRCA variants, lifestyle and ovarian cancer survival

ObjectiveWomen with ovarian cancer who have a pathogenic germline variant in BRCA1 or BRCA2 (BRCA) have been shown to have better 5-year survival after diagnosis than women who are BRCA-wildtype (non-carriers). Modifiable lifestyle factors, including smoking, physical activity and body mass index (BMI) have previously been associated with ovarian cancer survival; however, it is unknown whether these associations differ by germline BRCA status. MethodsWe investigated measures of lifestyle prior to diagnosis in two cohorts of Australian women with invasive epithelial ovarian cancer, using Cox proportional hazards regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsIn the combined studies (n = 1923), there was little association between physical activity, BMI or alcohol intake and survival, and no difference by BRCA status. However, the association between current smoking status before diagnosis and poorer survival was stronger for BRCA variant carriers (HR 1.98; 95% CI 1.20–3.27) than non-carriers (HR 1.18; 95% CI 0.96–1.46; p-interaction 0.02). We saw a similar differential association with smoking when we pooled results from two additional cohorts from the USA and UK (n = 2120). Combining the results from all four studies gave a pooled-HR of 1.94 (95% CI 1.28–2.94) for current smoking among BRCA variant carriers compared to 1.08 (0.90–1.29) for non-carriers. ConclusionsOur results suggest that the adverse effect of smoking on survival may be stronger for women with a BRCA variant than those without. Thus, while smoking cessation may improve outcomes for all women with ovarian cancer, it might provide a greater benefit for BRCA variant carriers.

A risk model of gene signatures for predicting platinum response and survival in ovarian cancer

BackgroundOvarian cancer (OC) is the deadliest tumor in the female reproductive tract. And increased resistance to platinum-based chemotherapy represents the major obstacle in the treatment of OC currently. Robust and accurate gene expression models are crucial tools in distinguishing platinum therapy response and evaluating the prognosis of OC patients.MethodsIn this study, 230 samples from The Cancer Genome Atlas (TCGA) OV dataset were subjected to mRNA expression profiling, single nucleotide polymorphism (SNP), and copy number variation (CNV) analysis comprehensively to screen out the differentially expressed genes (DEGs). An SVM classifier and a prognostic model were constructed using the Random Forest algorithm and LASSO Cox regression model respectively via R. The Gene Expression Omnibus (GEO) database was applied as the validation set.ResultsForty-eight differentially expressed genes (DEGs) were figured out through integrated analysis of gene expression, single nucleotide polymorphism (SNP), and copy number variation (CNV) data. A 10-gene classifier was constructed which could discriminate platinum-sensitive samples precisely with an AUC of 0.971 in the training set and of 0.926 in the GEO dataset (GSE638855). In addition, 8 optimal genes were further selected to construct the prognostic risk model whose predictions were consistent with the actual survival outcomes in the training cohort (p = 9.613e-05) and validated in GSE638855 (p = 0.04862). PNLDC1, SLC5A1, and SYNM were then identified as hub genes that were associated with both platinum response status and prognosis, which was further validated by the Fudan University Shanghai cancer center (FUSCC) cohort.ConclusionThese findings reveal a specific risk model that could serve as effective biomarkers to identify patients’ platinum response status and predict survival outcomes for OC patients. PNLDC1, SLC5A1, and SYNM are the hub genes that may serve as potential biomarkers in OC treatment.

Ovarian cancer in southeastern of Yemen

Introduction: Ovarian cancer is an important cause of mortality in women. The incidence of ovarian cancer and survival rates are still relatively unknown in southeast Yemen. This study takes into account trends in ovarian cancer incidence and survival rates by examining age, histological subtypes, residency, and treatment. Methods: The National Cancer Center Aden is the premier cancer care transformation center in the southeastern governorates and the source for collecting data on ovarian cancer mortality from 2014-2020 from the Surveillance, Epidemiology and End Results Database. The age-adjusted incidence rate, the percentage incidence rate, the annual percentage changes (APC) by histopathology and age at diagnosis were calculated. The 5-year survival rates were calculated by stage and treatment. Results: Mean age at presentation: 48.14 years (SD 15, range 20-79 years); commonest histological sub-type: presentation of OVC types was the Serous cystadenocarcinoma 56(34%); The most frequently seen stage: 4 (53%) of all ovarian cancers), followed by stage 3 (28%). The mortality rate for women with ovarian cancer is slightly higher in the years studied. Mortality was higher during period of the war. Conclusions: Due to the lack of adequate information on the epidemiological records of ovarian cancer in Yemen, there is an urgent need to carry out a large population study in southeastern Yemen in order to improve the programs of prevention and control of ovarian cancer in the region by the support of Ministry of Health and the World Health Organization.

T-cell activation is associated with high-grade serous ovarian cancer survival.

High-grade serous ovarian cancer (HGSOC) is an aggressive disease that is largely resistant to today's immunotherapies. Here, we aimed to investigate the prognostic significance of CTLA4, PD-1, and T-cell activation status in HGSOC. Using a publicly accessed microarray dataset including 260 HGSOC samples, we calculated Kaplan-Meier survival curves for overall survival (OS), evaluated associations with multivariate Cox regression models to evaluate the associations, and summarized using a hazard ratio (HR). The correlations between PD-1 gene expression and that of other genes were calculated by Pearson correlation. Multivariate survival analyses showed that high PD-1 expression but not CTLA4 was associated with longer OS (HR=0.69; 95% confidence interval [CI]=0.52-0.91; p=0.01), and that higher T-cell activation score was associated with better outcome (HR=0.74; 95% confidence interval [CI]=0.58-0.95; p=0.02). The top three PD-1 highly correlated genes were SIRPG (r=0.90, p < 2E-16), FASL (r=0.89, p < 2E-16), and CD8a (r=0.87, p < 2E-16). HGSOC patients' OS is positively associated T-cell activation score and PD-1 expression but not CTLA4. T cell activation score may serve as a candidate for personalized immunotherapy in HGSOC. The application of anti-PD-1 therapy to HGSOC should be cautious.

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RNA Drugs

CXCL9 inhibits tumour growth and drives anti-PD-L1 therapy in ovarian cancer

BackgroundResponse to immune checkpoint blockade (ICB) in ovarian cancer remains disappointing. Several studies have identified the chemokine CXCL9 as a robust prognosticator of improved survival in ovarian cancer and a characteristic of the immunoreactive subtype, which predicts ICB response. However, the function of CXCL9 in ovarian cancer has been poorly studied.MethodsImpact of Cxcl9 overexpression in the murine ID8-Trp53−/− and ID8-Trp53−/–Brca2−/− ovarian cancer models on survival, cellular immune composition, PD-L1 expression and anti-PD-L1 therapy. CXCL9 expression analysis in ovarian cancer subtypes and correlation to reported ICB response.ResultsCXCL9 overexpression resulted in T-cell accumulation, delayed ascites formation and improved survival, which was dependent on adaptive immune function. In the ICB-resistant mouse model, the chemokine was sufficient to enable a successful anti-PD-L1 therapy. In contrast, these effects were abrogated in Brca2-deficient tumours, most likely due to an already high intrinsic chemokine expression. Finally, in ovarian cancer patients, the clear-cell subtype, known to respond best to ICB, displayed a significantly higher proportion of CXCL9high tumours than the other subtypes.ConclusionsCXCL9 is a driver of successful ICB in preclinical ovarian cancer. Besides being a feasible predictive biomarker, CXCL9-inducing agents thus represent attractive combination partners to improve ICB in this cancer entity.

Distinct Genomic Profiles Are Associated with Treatment Response and Survival in Ovarian Cancer.

Simple SummaryIn most patients with ovarian cancer, their disease eventually becomes resistant to chemotherapy. The timing and type of treatment given are therefore highly important. Currently, treatment choice is mainly based on the subtype of cancer (from a histological point of view), prior response to chemotherapy, and the time it takes for the disease to recur. In this study, we combined complete genome data of the tumor with clinical data to better understand treatment responses. In total, 132 tumor samples were included, all from patients with disease that had spread beyond the primary location. By clustering the samples based on genetic characteristics, we have identified subgroups with distinct response rates and survival outcomes. We suggest that in the future, this data can be used to make more informed treatment choices for individuals with ovarian cancer.The majority of patients with ovarian cancer ultimately develop recurrent chemotherapy-resistant disease. Treatment stratification is mainly based on histological subtype and stage, prior response to platinum-based chemotherapy, and time to recurrent disease. Here, we integrated clinical treatment, treatment response, and survival data with whole-genome sequencing profiles of 132 solid tumor biopsies of metastatic epithelial ovarian cancer to explore genome-informed stratification opportunities. Samples from primary and recurrent disease harbored comparable numbers of single nucleotide variants and structural variants. Mutational signatures represented platinum exposure, homologous recombination deficiency, and aging. Unsupervised hierarchical clustering based on genomic input data identified specific ovarian cancer subgroups, characterized by homologous recombination deficiency, genome stability, and duplications. The clusters exhibited distinct response rates and survival probabilities which could thus potentially be used for genome-informed therapy stratification for more personalized ovarian cancer treatment.

Hyperspectral Imaging for Tissue Classification after Advanced Stage Ovarian Cancer Surgery-A Pilot Study.

Simple SummarySurvival of ovarian cancer patients largely relies on the surgical removal of all cancer cells. To achieve this, good vision is crucial. In this study, we evaluate the ability of hyperspectral imaging to detect ovarian cancer. Images of surgically removed tissue samples of 11 patients were taken and compared to histopathology in order to train machine learning software. For training purposes, only healthy tissues and tissues with high tumor cell content (>50%) were included. In total, 26 tissue samples and 26,446 data points of 10 patients were included. Tissue classification as either tumorous or healthy was evaluated by leave-one-out cross-validation. This resulted in a power of 0.83, a sensitivity of 0.81, a specificity of 0.70 and a Matthew’s correlation coefficient of 0.41. To conclude, this study shows that hyperspectral imaging can be used to recognize ovarian cancer. In the future, the technique may enable real-time image guidance during surgery.The most important prognostic factor for the survival of advanced-stage epithelial ovarian cancer (EOC) is the completeness of cytoreductive surgery (CRS). Therefore, an intraoperative technique to detect microscopic tumors would be of great value. The aim of this pilot study is to assess the feasibility of near-infrared hyperspectral imaging (HSI) for EOC detection in ex vivo tissue samples. Images were collected during CRS in 11 patients in the wavelength range of 665–975 nm, and processed by calibration, normalization, and noise filtering. A linear support vector machine (SVM) was employed to classify healthy and tumorous tissue (defined as >50% tumor cells). Classifier performance was evaluated using leave-one-out cross-validation. Images of 26 tissue samples from 10 patients were included, containing 26,446 data points that were matched to histopathology. Tumorous tissue could be classified with an area under the curve of 0.83, a sensitivity of 0.81, a specificity of 0.70, and Matthew’s correlation coefficient of 0.41. This study paves the way to in vivo and intraoperative use of HSI during CRS. Hyperspectral imaging can scan a whole tissue surface in a fast and non-contact way. Our pilot study demonstrates that HSI and SVM learning can be used to discriminate EOC from surrounding tissue.

LINC01234 regulates microRNA-27b-5p to induce the migration, invasion and self-renewal of ovarian cancer stem cells through targeting SIRT5

ABSTRACT LINC01234 has been suggested to correlate with the survival of ovarian cancer (OS), but its role in the properties of OC stem cells (OCSCs) has been rarely described. We aim to investigate the effect of LINC01234 on the differentiation and self-renewal of OCSCs through adsorption of microRNA (miR)-27b-5p to target sirtuins 5 (SIRT5). Expression of LINC01234 and SIRT5 in OC and normal samples included in TCGA and GTEx was searched through the GEPIA2 database. Bioinformatics analysis was conducted to predict the relation of LINC01234, miR-27b-5p and SIRT5. Expression of LINC01234, miR-27b-5p and SIRT5 in OC tissues and cells was detected. OCSCs were cultured and identified. CD133+ OCSCs were introduced with related oligonucleotides or vectors of LINC01234 or miR-27b-5p and SIRT5 to figure out their roles in OCSCs progression and tumorigenesis in vivo. The interaction of miR-27b-5p with LINC01234 or SIRT5 was analyzed. Bioinformatics analysis suggested that LINC01234 was very likely to influence SIRT5 and regulate the development of OC through miR-27b-5p. Up-regulated LINC01234 exhibited in OC tissues and cells. Down-regulated LINC01234 or elevated miR-27b-5p suppressed OCSCs progression and tumorigenesis in vivo. LINC01234 could restore SIRT5 expression by binding to miR-27b-5p. Down-regulated miR-27b-5p reversed the effect of silenced LINC01234 on OCSCs development and tumorigenesis in vivo. Up-regulation of SIRT5 reduced the effects of elevated miR-27b-5p on OCSCs progression and tumorigenesis in vivo. LINC01234 regulates miR-27b-5p to induce the migration, invasion and self-renewal of OCSCs through targeting SIRT5.

Metformin Use and Mortality in Women with Ovarian Cancer: An Updated Meta-Analysis.

Background Previous observational studies and meta-analysis suggested a possible association between metformin use and reduced mortality in women with ovarian cancer (OC). However, clinical factors that may influence the relationship remain poorly evaluated. We performed an updated meta-analysis to systematically evaluate the above association and to observe the potential influences of study characteristics on the association. Methods Relevant studies reporting the association between metformin use and mortality in women with OC in the multivariate adjusted model were identified by search of electronic databases that included PubMed, Embase, and Web of Science. The random-effects model was adopted to combine the results. Results Nine studies including 10030 women with OC were included. Overall, metformin use was independently associated with reduced overall mortality (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55–0.93, P=0.01; I2 = 62%). Consistent results were observed for studies comparing metformin users with nondiabetic women and studies comparing metformin users with diabetic women who did not use metformin (P for subgroup analysis = 0.70). Further subgroup analyses showed consistent results in studies with metformin use before or after the diagnosis of OC, with or without adjustment of body mass index (BMI) and with or without adjustment of concurrent medications (P for subgroup analyses all >0.10). Conclusion Metformin use is associated with reduced mortality in women with OC, which may be independent of the diabetic status of the controls, timing of metformin use, or adjustment of BMI and concurrent medications. Clinical trials are needed to validate the potential benefits of metformin on survival of OC.

Disparity of ovarian cancer survival between urban and rural settings

ObjectiveTo determine if there is a difference in overall survival of patients with epithelial ovarian cancer in rural, urban, and metropolitan settings in the United States.MethodsWe performed a retrospective cohort...

Downregulation of Methyltransferase-Like 14 Promotes Ovarian Cancer Cell Proliferation Through Stabilizing TROAP mRNA.

Altered expression levels of the proteins that regulate N6-methyladenosine (m6A) RNA methylation, including methyltransferase-like 14 (METTL14), are associated with cancer development. Based on our analysis of m6A methylation regulators using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we focused on the regulatory role of METTL14 in ovarian cancer. We performed bioinformatics and survival analyses with these datasets and also used METTL14-overexpressing SKOV-3 ovarian cancer cells for in vitro studies. Trophinin associated protein (TROAP) siRNA and treatment with or without actinomycin D was used in the cells for qRT-PCR, western blot, cDNA microarray, cell viability, colony formation, luciferase gene reporter, methylated RNA immunoprecipitation (MeRIP)-qPCR, total RNA methylation, and RNA stability assays. Additionally, ovarian cancer and normal tissue samples were analyzed by immunohistochemistry, qRT-PCR, and western blot assays. The TCGA and GEO data confirmed copy number variations (CNVs) of these m6A RNA methylation regulators in ovarian cancer tissues. Furthermore, reduced METTL14 expression was associated with alterations in CNVs as well as poor patient survival in ovarian cancer. Moreover, the METTL14 and m6A RNA methylation levels were both significantly reduced in ovarian cancer tissues than in normal tissues. Restoration of METTL14 expression suppresses ovarian cancer cell proliferation by inhibition of TROAP expression. Further in vivo and in vitro experiments confirmed that METTL14 is a negative regulator of ovarian cancer cell proliferation via TROAP expression and that m6A RNA methylation regulates TROAP mRNA stability. In conclusion, METTL14 overexpression decreased ovarian cancer proliferation by inhibition of TROAP expression via an m6A RNA methylation-dependent mechanism.

Up-regulation of MTHFD2 is associated with clinicopathological characteristics and poor survival in ovarian cancer, possibly by regulating MOB1A signaling

BackgroundMTHFD2 is a folate-coupled metabolic enzyme, which has been proved to participant in the metabolic reprogramming and tumor cell-sustaining proliferative capacity. However, the function of MTHFD2 in the development of ovarian cancer and its potential molecular mechanisms is still unclear.Materials and methodsThe expression, various mutations, prognosis, and related network signaling pathways of MTHFD2 were analyzed using bioinformatics-related websites, including Oncomine, GEPIA, UCSC, cBioPortal, KM Plotter, TISIDB and TIMER. The prognostic value of MTHFD2 expression was validated by our own ovarian cancer samples using RT-qPCR. The migration ad invasion of ovarian cancer cells were further analyzed by CCK-8 and transwell assay. The Western-blot assay was performed to explore the protein levels of MTHFD2 and MOB1A.ResultsWe obtained the following important results. (1) MTHFD2 expression was markedly up-regulated in ovarian cancer than normal samples. (2) Among patients with ovarian cancer, those with higher MTHFD2 expression was associated with lower survival rate. (3) The major mutation type of MTHFD2 in ovarian cancer samples was missense mutation. (4) MTHFD2 knockdown inhibited proliferation, migration, invasion, as well as the expression of MOB1A in vitro.ConclusionMTHFD2, as a NAD + -dependent enzyme, accelerated tumor progression by up-regulating MBO1A, suggesting that this protein may be an independent prognostic factor and a potential therapeutic target for future ovarian cancer treatments.

In Silico Study to Predict the Structural and Functional Consequences of SNPs on Biomarkers of Ovarian Cancer (OC) and BPA Exposure-Associated OC

Background: Recently, we have shown that seven genes, namely GBP5, IRS2, KRT4, LINCOO707, MRPL55, RRS1 and SLC4A11, have prognostic power for the overall survival in ovarian cancer (OC). Methods: We present an analysis on the association of these genes with any phenotypes and mutations indicative of involvement in female cancers and predict the structural and functional consequences of those SNPS using in silico tools. Results: These seven genes present with 976 SNPs/mutations that are associated with human cancers, out of which 284 related to female cancers. We have then analysed the mutation impact on amino acid polarity, charge and water affinity, leading to the identification of 30 mutations in gynaecological cancers where amino acid (aa) changes lead to opposite polarity, charges and water affinity. Out of these 30 mutations identified, only a missense mutation (i.e., R831C/R804C in uterine corpus endometrial carcinomas, UCEC) was suggestive of structural damage on the SLC4A11 protein. Conclusions: We demonstrate that the R831C/R804C mutation is deleterious and the predicted ΔΔG values suggest that the mutation reduces the stability of the protein. Future in vitro studies should provide further insight into the role of this transporter protein in UCEC.

Ayurveda Maintenance Therapy in Recurrent Ovarian Cancer

AbstractDespite optimal surgery and first-line platinum-based doublet chemotherapy, approximately 70 to 80% of patients with epithelial ovarian cancers relapse. Two cases of recurrent ovarian cancer (ROC) were treated with non–platinum-based Ayurveda maintenance therapy (AMT) consisting of drugs having a herbal and herbomineral origin. This regimen was followed over a period of 3 years and progression-free survival (PFS) was noted along with platinum-free interval (PFI). Two patients were diagnosed with BRCA1 mutated recurrent high-grade serous ovarian carcinoma and treated with the per-oral AMT regimen labeled as ZINCA-30 in our hospital after completion of standard of care treatment and followed up until progression. The ZINCA-30 regimen comprising Jasada (traditional Zinc preparation), Indukanth kwatham and Curcuma amada powder in combination was prescribed based on Rasayana chikitsa postulated in Ayurveda. The patients were followed up every 3 months. The progression-free survival observed in these patients was 28 months and 45 months, respectively. These two pilot cases suggested an increased platinum-free interval (PFI), improved progression-free survival (PFS) in recurrent ovarian cancer (ROC), with the AMT labeled as ZINCA-30 after chemotherapy.