Overall Survival In Ovarian Cancer Research Articles

Analysis of progression-free and overall survival in ovarian cancer: Bevacizumab treatment outcomes using historical cohort.

Background: The incorporation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has redefined therapeutic strategies for advanced ovarian cancer. This study evaluates the efficacy of bevacizumab combined with standard chemotherapy by comparing progression-free survival (PFS) and overall survival (OS) outcomes with a historical cohort of patients treated with standard chemotherapy alone. Methods: We conducted an analysis of 71 patients with advanced epithelial ovarian cancer treated at the University Clinical Center in Niš, Serbia, from April 2017 to March 2023. All patients received standard chemotherapy paired with bevacizumab and were monitored for progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Subgroup analyses were performed based on age, ECOG performance status, presence of metastases, and pleural effusion. Additionally, a historical cohort of 30 patients treated with standard chemotherapy alone was used for comparison, and Cox regression analysis was conducted to identify factors influencing treatment outcomes. Results: The study findings indicate significant improvements in median PFS (20 months vs. 15 months) and OS (58 months vs. an undetermined upper limit) compared to the historical cohort. Subgroup analysis of the bevacizumab-treated group revealed that younger patients (<65 years) and those without metastases or pleural effusion exhibited notably better survival outcomes. The hazard ratio for PFS in patients younger than 65 was 0.65 (95% CI: 0.45-0.93), suggesting a substantial reduction in disease progression risk compared to older patients. Conclusion: Bevacizumab, when used alongside standard chemotherapy, significantly extends both PFS and OS in patients with advanced ovarian cancer. These benefits are particularly pronounced in younger patients. The results underscore the necessity of integrating bevacizumab into the treatment regimen for advanced ovarian cancer, advocating for tailored therapeutic strategies based on individual risk profiles and clinical characteristics. This study reinforces the pivotal role of bevacizumab in enhancing the current ovarian cancer treatment landscape and highlights the potential for further personalizing oncological care.

Charlson’s comorbidity and remission outcomes in women diagnosed with epithelial ovarian cancer.

e17562 Background: Several prior studies have examined the role of comorbidity on overall survival in ovarian cancer (OC) patients and reported an association between comorbidity and inferior overall survival. However, it is unclear if the inferior survival was solely due to the excess mortality from the comorbidities, or that the comorbidities can impact OC treatment outcomes. Our objective was to determine whether pre-existing Charlson comorbidity index (CCI) was associated with lower likelihood of achieving complete remission. Methods: This retrospective cohort study included patients diagnosed with OC of epithelial subtype between 01/01/2017-06/30/2021 at a large integrated healthcare delivery system in the United States. OC patients were identified from the healthcare system’s cancer registry or via chart review of those with the ICD-10 diagnosis code. Patient’s CCI was determined based on data from the 12-month window prior to OC diagnosis. Patients’ remission outcomes, including complete remission and clinical remission (complete + partial remission) were ascertained via chart review, considering physician’s assessment, CA125 value and imaging evidence. Data on potential confounders (pandemic period, age, race/ethnicity, FIGO stage, prior length of membership, and time to treatment) were obtained from the healthcare system’s electronic medical records. Bivariate and multivariable modified Poisson regressions adjusting for potential confounders were used to evaluate the associations between CCI and achieving complete remission or clinical remission by end of therapy. Results: A total of 799 patients diagnosed with OC were included in our study. Overall, the cohort was racially/ethnically diverse with 46.2% White, 33.8% Hispanic, 12.4% Asian, and 7.6% Black patients. In the crude analysis, those with CCI score=1 and CCI≥2 had lower likelihood of achieving complete remission, compared with those with CCI=0 (no Charlson comorbidity) [RR= 0.84 (0.76-0.93) and RR=0.72 (0.64-0.81), respectively]. In the multivariable analysis, those with CCI=1 and CCI≥2 continued to have lower likelihood of achieving complete remission, compared with those with CCI= 0 [RR= 0.84 (0.77-0.92) and RR=0.81 (0.72-0.91), respectively]. Similar findings were observed for clinical remission, although the associations were attenuated: RR= 0.95 (0.89-1.01) for CCI=1 and RR=0.92 (0.86-1.00) for CCI≥2 vs. CCI=0. Conclusions: Having Charlson comorbidity was associated with lower likelihood of achieving complete remission in OC patients. This finding suggest that pre-existing comorbidities may contribute to inferior survival via, at least in part, adversely affecting the likelihood of achieving complete remission. The potential mechanisms underlying this association should be further studied to inform patient management.

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio as an Early Prognostic Marker in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis.

Presently, ovarian cancer remains the leading cause of death in gynecological malignancies. The survival rate of these patients is low, which might be caused by early metastases and delayed diagnosis. Therefore, it is crucial to investigate novel practical markers that provide early prognostic value which helps construct individualized treatment. A thorough investigation of the neutrophil-lymphocyte ratio (NLR) and lymphocyte ratio (PLR) in ovarian cancer patients was conducted using article selection from PubMed, Cochrane, Science Direct, and Google Scholar databases. The outcomes and hazard ratio (HR) were obtained using Review Manager 5.4, and the 95% Confidence Interval (CI) result was calculated. The chief endpoints of interest in this study include overall survival (OS) and progression-free survival (PFS). Sixteen studies with 3,862 patients were included with a mean age of 50.6 years and a mean follow-up of 45.84 months. Multivariate studies demonstrated that a higher NLR is associated with worse PFS and OS, HR 1.35;95% CI [1.05-1.74] and HR 1.46; 95% CI [1.16-1.83] respectively. Similar results are observed with PLR and poorer PFS and OS, HR 1.62; 95% CI [1.09-2.43] and HR 1.66; 95% CI [1.12-2.46]. Pre-treatment PLR and NLR were found to be prognostic factors in determining PFS and OS in ovarian cancer. High values in pre-treatment PLR and NLR may indicate worse clinical outcomes.

Immune-related gene methylation prognostic instrument for stratification and targeted treatment of ovarian cancer patients toward advanced 3PM approach.

DNA methylation is an important mechanism in epigenetics, which can change the transcription ability of genes and is closely related to the pathogenesis of ovarian cancer (OC). We hypothesize that DNA methylation is significantly different in OCs compared to controls. Specific DNA methylation status can be used as a biomarker of OC, and targeted drugs targeting these methylation patterns and DNA methyltransferase may have better therapeutic effects. Studying the key DNA methylation sites of immune-related genes (IRGs) in OCpatients and studying the effects of these methylation sites on the immune microenvironment may provide a new method for further exploring the pathogenesis of OC, realizing early detection and effective monitoring of OC, identifying effective biomarkers of DNA methylation subtypes and drug targets, improving the efficacy of targeted drugs or overcoming drug resistance, and better applying it to predictive diagnosis, prevention, and personalized medicine (PPPM; 3PM) of OC. Hypermethylated subtypes (cluster 1) and hypomethylated subtypes (cluster 2) were established in OCs based on the abundance of different methylation sites in IRGs. The differences in immune score, immune checkpoints, immune cells, and overall survival were analyzed between different methylation subtypes in OC samples. The significant pathways, gene ontology (GO), and protein-protein interaction (PPI) network of the identified methylation sites in IRGs were enriched. In addition, the immune-related methylation signature was constructed with multiple regression analysis. A methylation site model based on IRGs was constructed and verified. A total of 120 IRGs with 142 differentially methylated sites (DMSs) were identified. The DMSs were clustered into a high-level methylation group (cluster 1) and a low-level methylation group (cluster 2). The significant pathways and GO analysis showed many immune-related and cancer-associated enrichments. A methylation site signature based on IRGs was constructed, including RORC|cg25112191, S100A13|cg14467840, TNF|cg04425624, RLN2|cg03679581, and IL1RL2|cg22797169. The methylation sites of all five genes showed hypomethylation in OC, and there were statistically significant differences among RORC|cg25112191, S100A13|cg14467840, and TNF|cg04425624 (p < 0.05). This prognostic model based on low-level methylation and high-level methylation groups was significantly linked to the immune microenvironment as well as overall survival in OC. This study provided different methylation subtypes for OC patients according to the methylation sites of IRGs. In addition, it helps establish a relationship between methylation and the immune microenvironment, which showed specific differences in biological signaling pathways, genomic changes, and immune mechanisms within the two subgroups. These data provide ones to deeply understandthe mechanism of immune-related methylation genes on the occurrence and development of OC. The methylation-site signature is also to establish new possibilities for OC therapy. These data are a precious resource for stratification and targeted treatment of OC patients toward an advanced 3PM approach. The online version contains supplementary material available at 10.1007/s13167-024-00359-3.

Epithelial IL-8 immunostaining associated with overall survival in ovarian cancer

Epithelial IL-8 immunostaining associated with overall survival in ovarian cancer

Prognostic Factors Influencing Survival in Ovarian Cancer Patients: A 10-Year Retrospective Study.

To analyze the factors associated with overall survival (OS) and progression-free survival (PFS) in patients with ovarian cancer in Cyprus. We retrospectively analyzed data from patients with histologically confirmed epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). A total of 106 women diagnosed with ovarian cancer were included, with a median age at diagnosis of 58 years. The Kaplan-Meier survival analysis showed a median OS of 41 months (95% C.I = 36.9, 45.1), and the FIGO stage (p < 0.001), type of surgery (p < 0.001) and performance status (p < 0.001) were identified as statistically significant prognostic factors for OS. PFS analysis revealed the FIGO stage (p = 0.006) and the performance status (p < 0.001) as significant prognostic factors. Additionally, a Cox regression analysis for median OS was performed for patients with high-grade serous carcinoma, identifying the performance status, FIGO stage, and type of surgery as prognostic factors in univariate analysis. However, in the subsequent multivariate analysis, the performance status and the FIGO stage were confirmed to be the only statistically significant prognostic factors for OS (p < 0.05). This study confirms that the FIGO stage, performance status, and surgery type were considered as prognostic factors for OS in ovarian cancer.

MUM1L1 as a Tumor Suppressor and Potential Biomarker in Ovarian Cancer: Evidence from Bioinformatics Analysis and Basic Experiments.

Ovarian cancer (OC) is the most prevalent gynecologic malignancy, with high mortality rates. However, its pathogenesis remains unclear. The current study aimed to explore potential biomarkers and suppressor genes for diagnosing and treating OC. Biochemical and bioinformatics approaches were used to detect differentially expressed genes (DEGs) in ovarian tissues via integration analysis. Kaplan-Meier plot analysis was performed to assess progression-free survival and overall survival according to DEGs. Then, we constructed a protein-protein interaction (PPI) network based on data from the STRING database to identify the related target genes of DEGs. Finally, DEGs regulating the proliferation, migration, and invasion of SKOV3 cell lines were validated via in vitro experiments. Four DEGs (MUM1L1, KLHDC8A, CRYGD, and GREB1) with enriched expression in ovarian tissues were explicitly expressed in the ovary based on an analysis of all human proteins. MUM1L1 had high specificity, and its expression was higher in normal ovarian tissues than in OC tissues. Kaplan-Meier plot analysis showed that a high MUM1L1 expression was associated with longer progression-free survival and overall survival in OC. Based on the PPI analysis results, CBLN4, CBLN1, PTH2R, TMEM255B, and COL23A1 were associated with MUM1L1. In vitro studies revealed that MUM1L1 overexpression decreased the proliferation, migration, and invasion ability of SKOV3 cell lines. Meanwhile, MUM1L1 knockdown had contrasting results. MUM1L1 is a tumor suppressor gene and is a potential biomarker for diagnosing and treating OC.

Identification of N1 methyladenosine-related biomarker predicting overall survival outcomes and experimental verification in ovarian cancer.

This study aimed to construct a N1-methyladenosine (m1A)-related biomarker model for predicting the prognosis of ovarian cancer (OVCA). OVCA samples were clustered into two subtypes using the Non-Negative Matrix Factorization (NMF) algorithm, including TCGA (n = 374) as the training set and GSE26712 (n = 185) as the external validation set. Hub genes, which were screened to construct a risk model, and nomogram to predict the overall survival of OVCA were explored and validated through various bioinformatic analysis and quantitative real-time PCR. Following bootstrap correction, the C-index of nomogram was 0.62515, showing reliable performance. The functions of DEGs in the high- and low-risk groups were mainly enriched in immune response, immune regulation, and immune-related diseases. The immune cells relevant to the expression of hub genes were explored, for example, Natural Killer (NK) cells, T cells, activated dendritic cells (aDC). AADAC, CD38, CACNA1C, and ATP1A3 might be used as m1A-related biomarkers for OVCA, and the nomogram labeled with m1A for the first time had excellent performance for predicting overall survival in OVCA.

Bioinformatics analysis of the clinicopathological and prognostic significance of BAG3 mRNA in gynecological cancers

BAG3 is a co-chaperone BAG family protein that plays important roles in protein homeostasis, cell survival, cell motility, and tumour metastasis. This study aimed to clarify the clinicopathological and prognostic implications of BAG3 mRNA expression in tumours. We performed bioinformatics analysis on BAG3 mRNA expression using TCGA, XIANTAO, UALCAN, and Kaplan-Meier plotter databases. BAG3 mRNA expression was downregulated in breast and endometrial cancers and positively correlated with favourable PAM50 subtyping in breast cancer，clinical stage and short overall survival in ovarian cancer and negatively correlated with T stage, clinical stage, and histological grade in cervical and endometrial cancers. The top BAG3-related pathways included ligand-receptor interactions and activity, DNA packaging and nucleosomes, hormonal responses, membrane regions, microdomains and rafts, and endosomes in breast cancer; ligand-receptor interactions, transmembrane transporters and channels, cell adhesion, and keratinisation in cervical cancer; ligand-receptor interactions, anion transmembrane transporters, lipoproteins, keratinisation, cell adhesion, and protein processing in endometrial cancer; metabolism of porphyrin, chlorophyll, pentose, uronic acid, ascorbate, and alternate and cell adhesion in ovarian cancer. BAG3 expression could represent a potential marker for carcinogenesis, histogenesis, aggressive behaviours, and prognosis in gynecological cancers. IMPACT STATEMENT What is already known on this subject? BAG3 regulates cell activity, autophagy, and resistance to apoptosis through multiple domains and plays an important role in tumour development. BAG3 positively regulates tumour cell invasion and migration in cervical and ovarian cancers. What do the results of this study add? BAG3 expression is closely associated with histogenesis, clinicopathology, and prognosis in gynecological cancers and is involved in signalling pathways associated with the control of cell proliferation, migration, invasion, and drug resistance in tumours. What are the implications of these findings for clinical practice and/or further research? Abnormal BAG3 expression can be employed as a possible marker of tumour development, invasion, and prognosis, providing new ideas for treating cancer.

Chemotherapeutic sensitivity in colorectal cancer expressing low RNA of wild type homologous recombination genes.

3531 Background: Homologous recombination deficient (HRD) colorectal cancer (CRC) has improved overall survival (OS) when exposed to DNA damaging agents (DDA) oxaliplatin (OX) and irinotecan (IR). However, this OS benefit is only observed in HRD mutated CRC. Low expression of wild type (WT) BRCA1 RNA displays prolonged OS in ovarian cancer; this finding has not been investigated in CRC or outside BRCA. We investigate if low expression of WT HR genes is associated with prolonged OS in response to DDA. Methods: A total of 12,860 CRC patients tumor biopsies were analyzed by next-generation sequencing (592, NextSeq; WES, WTS NovaSeq). Patients with HRD mutations and MSI-H were excluded (N = 935). 11,925 patients were included in the analysis. A total of 11 core ( BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B) and 7 related ( BAP1, WRN, DNMT3A, ERCC1, FANCA, FANCF, RECQL4) HR genes were analyzed. Samples were classified by RNA expression percentiles within the studied cohort. Real world OS was extracted from insurance claims and calculated using Kaplan-Meier estimates for molecularly defined cohorts from first of OX or IR to last contact. Results: OS benefit is seen in low RNA expression (bottom 10%) compared to high expression (top 10%) of all core WT HR genes except RAD51B, BARD1 and BRCA2 in response to IR. We observe a progressively longer OS with lower associated RNA expression in response to DDA. OS of nearly 7 years was observed in low expressing BRCA1 and RAD51 following IR exposure and 4.5-year OS benefit when compared to high expression of these genes. OS benefit in response to OX was less robust but significantly prolonged in BRCA1 and BRIP1 (Table). Patients harboring HRD mutations had similar OS to WT HR RNA low (bottom 10%) in response to OX (HR = 0.75; p = 0.1) and IR (HR = 0.82; p = 0.36). Conclusions: Here we report a novel subclass of CRC defined as patients with low RNA expressing WT HR genes that exhibit differential sensitivity to DDA. Significantly longer survival is noted in CRC with low expression BRCA1, RAD51 and BLM, while post-OX survival was significantly prolonged with low expression of BRCA1, BRIP1 and FANCA. Further characterization of sensitive HR genes will better predict DDA sensitivity and impact treatment sequencing. [Table: see text]

Pan-cancer associations of B7-H3 (CD276) transcriptional expression across human malignancies.

2624 Background: B7-H3 ( CD276) is a transmembrane glycoprotein of the B7 superfamily that includes PD-L1 and CTLA-4. B7-H3 targeted therapeutics have demonstrated promising results in both solid tumors and hematologic cancers. To understand the applicability of B7-H3 targeted therapies, we characterized the landscape of clinical outcomes, genomic, transcriptomic, and immunological features associated with B7-H3 mRNA expression in &gt; 93,000 samples across &gt; 45 cancer types from a large real-world clinico-genomics database. Methods: DNA (592-gene/whole exome) and RNA (whole transcriptome) sequencing was performed for samples submitted to Caris Life Sciences (Phoenix, AZ). Differential expression of individual genes was analyzed, with pathway enrichment assessed by Gene Set Enrichment Analyses (GSEA). RNA deconvolution was used to estimate immune cell infiltration of tumor microenvironments using quanTIseq (Finotello, 2019). Real-world overall survival (OS) was determined from insurance claims data and Kaplan-Meier estimates were calculated. Statistical significance was determined using X2 and Mann-Whitney U tests with Benjamini-Hochberg corrections for multiple hypothesis testing where appropriate. Results: B7-H3 mRNA displayed robust expression in many prevalent cancer types, including prostate, pancreatic, breast, colorectal, ovarian, and lung cancers (n = 3407, 4624, 8639, 12,862, 8004, and 13,502, respectively). High B7-H3 expression predicted worse OS in ovarian cancer (1.38 HR, 95% CI 1.23-1.53, p &lt; 0.001) and lung adenocarcinoma (1.45 HR, 95% CI 1.34-1.57, p &lt; 0.001), and better OS in prostate (0.84 HR, 95% CI 0.71-0.99, p &lt; 0.05). Notably, high B7-H3 was detected in tumors with known driver mutations (e.g. EGFR, ESR1, KRAS, SPOP) or undruggable therapeutic targets ( TP53, APC). When examining Hallmark gene signatures, we found that B7-H3-high samples demonstrated consistent enrichment for pathways involved in epithelial to mesenchymal transition (EMT), WNT, TGF-Beta, and Notch signaling (FDR &lt; 0.05) across cancer types. Additionally, high B7-H3 expression was correlated with greater proportions of pro-inflammatory M1 macrophages but lower proportions of effector CD8+ T cells and NK cells across multiple cancer types. Conclusions: We demonstrate B7-H3 to be a promising pan-tumor target, with most solid tumors showing robust expression which is often associated with worse OS. In several major cancers, high B7-H3 expression was associated with mutational and transcriptomic repertoires not easily targeted by current precision therapies. We find B7-H3-high tumors to have increased potential for myeloid-driven immune induction, making them potentially more amenable to immunomodulatory therapies, in particular, those targeting B7-H3. Further work is warranted to elucidate different mechanistic interactions of B7-H3 with specific oncogenic pathways in each cancer type.

PARP inhibitors and overall survival in ovarian cancer, reevaluation advised in all settings.

PARP inhibitors in ovarian cancer have been a breakthrough therapy of the past decade, driven by positive trial results, and supported by an original pharmacological rationale. However, with mature data, detrimental survival results led to the withdrawals, in 2022, of all approved PARP inhibitors in the most advanced settings' indication (as monotherapy in third or subsequent lines) by the US Food and Drug Administration (FDA). Two other indications, as maintenance after relapse, were also restricted. In this work, based on pooled meta-analysis in each setting, we question a unique situation in oncology: a survivalbenefit is seen in front-line settings, with, at the same time, a survivaldecrement in later lines. Either this original feature is explained by the unique biological action of PARP inhibitors-through synthetic lethality-in patients with ovarian cancer and homologous repair deficiency. Another explanation may be trial design: decrement in later lines could partly explain why beneficial results were seen in early settings, simply by avoiding late exposure to PARP inhibitors in the experimental arm in those trials. High crossover rates seen in some trials further support this alternate hypothesis. We contend our analysis and recent survival results of PARP inhibitors warrant a whole reassessment of the place of these compounds in the landscape of ovarian cancer treatments.

Prognostic Significance of the CXCLs and Its Impact on the Immune Microenvironment in Ovarian Cancer.

The chemokine (C-X-C motif) ligand (CXCL) family in tumor tissue is closely related to tumor growth, metastasis, and survival. However, the differential expression profile and prognostic value of the CXCLs in ovarian cancer (OC) have not been elucidated. Therefore, we studied the expression levels and mutations of CXCLs in OC patient in TCGA and various public databases. The expression differences of CXCLs in OC cancer tissues and normal tissues were compared through the Gene Expression Profiling Interactive Analysis (GEPIA) database. The effect of CXCLs on OC prognosis was analyzed using the Kaplan-Meier curves in GEPIA database. The impact of CXCLs on immune infiltration and clinicopathological outcomes in OC was assessed using the TIMER algorithm. Compared with normal tissues, we found that eight CXCLs were significantly differentially expressed in OC. The expression levels of CXCL9 (P = 0.0201), CXCL11 (P = 0.0385), and CXCL13 (P = 0.0288) were significantly associated with tumor stage. CXCL13 was the only gene that significantly affected both disease-free survival (DFS) and overall survival (OS) in OC, and higher CXCL13 transcript levels implied longer DFS and OS. Although there was no significant impact on DFS, CXCL10 (P = 0.0079) and CXCL11 (P = 0.0011) expression levels had a significant effect on OS in OC. At the same time, CXCLs were significantly associated with several immune-infiltrating cells in OC tissues. The CXCLs were significantly associated with one or more immune-infiltrating cells in OC tissue. CXCL13 was differentially expressed in OC and significantly affected the prognosis of patients and was a potential marker of OC prognosis.

Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer

BackgroundSerous ovarian carcinoma is the most frequent histological subgroup of ovarian cancer and the leading cause of death among gynecologic tumors. The tumor microenvironment and cancer-associated fibroblasts (CAFs) have a critical role in the origin and progression of cancer. We comprehensively characterized the crosstalk between CAFs and ovarian cancer cells from malignant fluids to identify specific ligands and receptors mediating intercellular communications and disrupted pathways related to prognosis and therapy response.MethodsMalignant fluids of serous ovarian cancer, including tumor-derived organoids, CAFs-enriched (eCAFs), and malignant effusion cells (no cultured) paired with normal ovarian tissues, were explored by RNA-sequencing. These data were integrated with single-cell RNA-sequencing data of ascites from ovarian cancer patients. The most relevant ligand and receptor interactions were used to identify differentially expressed genes with prognostic values in ovarian cancer.ResultsCAF ligands and epithelial cancer cell receptors were enriched for PI3K-AKT, focal adhesion, and epithelial-mesenchymal transition signaling pathways. Collagens, MIF, MDK, APP, and laminin were detected as the most significant signaling, and the top ligand-receptor interactions THBS2/THBS3 (CAFs)—CD47 (cancer cells), MDK (CAFs)—NCL/SDC2/SDC4 (cancer cells) as potential therapeutic targets. Interestingly, 34 genes encoding receptors and ligands of the PI3K pathway were associated with the outcome, response to treatment, and overall survival in ovarian cancer. Up-regulated genes from this list consistently predicted a worse overall survival (hazard ratio > 1.0 and log-rank P < 0.05) in two independent validation cohorts.ConclusionsThis study describes critical signaling pathways, ligands, and receptors involved in the communication between CAFs and cancer cells that have prognostic and therapeutic significance in ovarian cancer.AKQp7fCjRyS9LmaGP7R5S5Video abstract

MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer.

Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic cancer, etc. MSLN is considered to play an important role in cell survival, proliferation, and tumor progression. Although the expression of MSLN in tumors makes it a potential therapeutic target, its mechanism of action is still unclear, especially its correlation with immune cells infiltration in the tumor microenvironment has not been investigated. In this study, we detected the overexpression of MSLN in ovarian cancer using database analysis and tissue-array staining. We further evaluated the diagnostic value of MSLN and found it was associated with poor overall survival in ovarian cancer. In addition, the high expression of MSLN was significantly related to the immune-related genes and chemoresistant genes. We confirmed the overexpression of MSLN in the chemoresistant ovarian cancer cell lines. Our research suggests that MSLN participates in a variety of pathways related to the suppression of immune activation and promotion of chemoresistance, leading to a poor prognosis in ovarian cancer.

WASF2 Serves as a Potential Biomarker and Therapeutic Target in Ovarian Cancer: A Pan-Cancer Analysis.

BackgroundWiskott-Aldrich syndrome protein family member 2 (WASF2) has been shown to play an important role in many types of cancer. Therefore, it is worthwhile to further study expression profile of WASF2 in human cancer, which provides new molecular clues about the pathogenesis of ovarian cancer.MethodsWe used a series of bioinformatics methods to comprehensively analyze the relationship between WASF2 and prognosis, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and tried to find the potential biological processes of WASF2 in ovarian cancer. Biological behaviors of ovarian cancer cells were investigated through CCK8 assay, scratch test and transwell assay. We also compared WASF2 expression between epithelial ovarian cancer tissues and normal ovarian tissues by using immunohistochemical staining.ResultsIn the present study, we found that WASF2 was abnormally expressed across the diverse cancer and significantly correlated with overall survival (OS) and progression-free interval (PFI). More importantly, the WASF2 expression level also significantly related to the TME. Our results also showed that the expression of WASF2 was closely related to immune infiltration and immune-related genes. In addition, WASF2 expression was associated with TMB, MSI, and antitumor drugs sensitivity across various cancer types. Functional bioinformatics analysis demonstrated that the WASF2 might be involved in several signaling pathways and biological processes of ovarian cancer. A risk factor model was found to be predictive for OS in ovarian cancer based on the expression of WASF2. Moreover, in vitro experiments, it was demonstrated that the proliferative, migratory and invasive capacity of ovarian cancer cells was significantly inhibited due to WASF2 knockdown. Finally, the immunohistochemistry data confirmed that WASF2 were highly expressed in ovarian cancer.ConclusionsOur study demonstrated that WASF2 expression was associated with a poor prognosis and may be involved in the development of ovarian cancer, which might be explored as a potential prognostic marker and new targeted 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.

The Association between the Preoperative Prognostic Nutritional Index and the Controlling Nutritional Status Score on Tumor Stage, Chemotherapeutic Response and Overall Survival in Ovarian Cancer

Objective: This study aimed to investigate the association between preoperative prognostic nutritional index (PNI) and controlling nutritional status (CONUT) scores on the stage of ovarian cancer (OC), chemotherapeutic response, and overall survival (OS) in patients with OC. Methods: The data of the patients who operated due to OC between January 2015 and January 2020 in a tertiary referral hospital were recorded. The patients’ basic characteristics, preoperative total cholesterol, albumin, lymphocyte count, tumor markers, disease stage, grade, chemotherapeutic response, OS, and progression-free survival were recorded. The PNI and the CONUT score were calculated. Results: The mean PNI level was considerably higher in the early-stage group than the advanced-stage group (50.02 ± 6.8 vs. 46.3 ± 7.4, p = 0.005). The AUC was 63% for the cutoff point 45.98 of PNI, whereas the AUC was 42% for the cutoff point 1.5 of CONUT score in predicting early-stage disease. The PFS and OS were significantly higher in the high PNI group than the low PNI group (p = 0.01, p = 0.002, respectively). Conclusion: The patients with early-stage OC had significantly higher PNI levels and lower CONUT scores in our study population.

Construction and validation of a novel aging-related gene signature and prognostic nomogram for predicting the overall survival in ovarian cancer.

BackgroundOvarian cancer (OC) is the most lethal gynecological malignancy. The objective of this study was to establish and validate an individual aging‐related gene signature and a clinical nomogram that can powerfully predict independently the overall survival rate of patients with ovarian cancer.MethodsData on transcriptomic profile and relevant clinical information were retrieved from The Cancer Genome Atlas (TCGA) database as a training group, and the same data from three public Gene Expression Omnibus (GEO) databases as validation groups. Univariate Cox regression analysis, lasso regression analysis, and multiple multivariate Cox analysis were analyzed sequentially to select the genes to be included in the aging‐associated signature. A risk scoring model was established and verified, the predictive value of the model was evaluated, and a clinical nomogram was established.ResultsWe found eight genes that were most relevant to prognosis and constructed an eight‐mRNA signature. Based on the model, each OC patient's risk score was able to be calculated and patients were split into groups of low and high risks with a distinct outcome. Survival analysis confirmed that the outcome of patients in the high‐risk group was dramatically shorter than that of those in the low‐risk group, and the eight‐mRNA signature can be considered as a powerful and independent predictor that could predict the outcome of OC patient. Additionally, the risk score and age can be used to construct a clinical nomogram as a simpler tool for predicting prognosis. We also explored the association between the risk score and immunity and drug sensitivity.ConclusionThis study suggested that the aging‐related gene signature could be used as an intervention point and latent prognostic predictor in OC, which may provide new perceptions for postoperative treatment strategies.

Bevacizumab confers significant improvements in survival for ovarian cancer patients with low miR-25 expression and high miR-142 expression

BackgroundLymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients.MethodsThe Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset.ResultsWe showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status.ConclusionIn conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly.