A novel TCGA-validated programmed cell-death-related signature of ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is a gynecological malignancy tumor with high recurrence and mortality rates. Programmed cell death (PCD) is an essential regulator in cancer metabolism, whose functions are still unknown in OC. Therefore, it is vital to determine the prognostic value and therapy response of PCD-related genes in OC. METHODS: By mining The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Genecards databases, we constructed a prognostic PCD-related genes model and performed Kaplan-Meier (K-M) analysis and Receiver Operating Characteristic (ROC) curve for its predictive ability. A nomogram was created via Cox regression. We validated our model in train and test sets. Quantitative real-time PCR (qRT-PCR) was applied to identify the expression of our model genes. Finally, we analyzed functional analysis, immune infiltration, genomic mutation, tumor mutational burden (TMB) and drug sensitivity of patients in low- and high-risk group based on median scores. RESULTS: A ten-PCD-related gene signature including protein phosphatase 1 regulatory subunit 15 A (PPP1R15A), 8-oxoguanine-DNA glycosylase (OGG1), HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 (HERC1), Caspase-2.(CASP2), Caspase activity and apoptosis inhibitor 1(CAAP1), RB transcriptional corepressor 1(RB1), Z-DNA binding protein 1 (ZBP1), CD3-epsilon (CD3E), Clathrin heavy chain like 1(CLTCL1), and CCAAT/enhancer-binding protein beta (CEBPB) was constructed. Risk score performed well with good area under curve (AUC) (AUC3 - year =0.728, AUC5 - year = 0.730). The nomogram based on risk score has good performance in predicting the prognosis of OC patients (AUC1 - year =0.781, AUC3 - year =0.759, AUC5 - year = 0.670). Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that the erythroblastic leukemia viral oncogene homolog (ERBB) signaling pathway and focal adhesion were enriched in the high-risk group. Meanwhile, patients with high-risk scores had worse OS. In addition, patients with low-risk scores had higher immune-infiltrating cells and enhanced expression of checkpoints, programmed cell death 1 ligand 1 (PD-L1), indoleamine 2,3-dioxygenase 1 (IDO-1) and lymphocyte activation gene-3 (LAG3), and were more sensitive to A.443,654, GDC.0449, paclitaxel, gefitinib and cisplatin. Finally, qRT-PCR confirmed RB1, CAAP1, ZBP1, CEBPB and CLTCL1 over-expressed, while PPP1R15A, OGG1, CASP2, CD3E and HERC1 under-expressed in OC cell lines. CONCLUSION: Our model could precisely predict the prognosis, immune status and drug sensitivity of OC patients.

Racial and socioeconomic disparities in survival among women with advanced-stage ovarian cancer who received systemic therapy.

PURPOSE: The purpose of this study was to assess the association between race/ethnicity and all-cause mortality among women with advanced-stage ovarian cancer who received systemic therapy. METHODS: We analyzed data from the National Cancer Database on women diagnosed with advanced-stage ovarian cancer from 2004 to 2015 who received systemic therapy. Race/ethnicity was categorized as Non-Hispanic (NH) White, NH-Black, Hispanic, NH-Asian/Pacific Islander, and Other. Income and education were combined to form a composite measure of socioeconomic status (SES) and categorized into low-, mid-, and high-SES. Multivariable Cox proportional hazards models were used to assess whether race/ethnicity was associated with the risk of death after adjusting for sociodemographic, clinical, and treatment factors. Additionally, subgroup analyses were conducted by SES, age, and surgery receipt. RESULTS: The study population comprised 53,367 women (52.4% ages ≥ 65 years, 82% NH-White, 8.7% NH-Black, 5.7% Hispanic, and 2.7% NH-Asian/Pacific Islander) in the analysis. After adjusting for covariates, the NH-Black race was associated with a higher risk of death versus NH-White race (aHR: 1.12; 95% CI: 1.07,1.18), while Hispanic ethnicity was associated with a lower risk of death compared to NH-White women (aHR: 0.87; 95% CI: 0.80, 0.95). Furthermore, NH-Black women versus NH-White women had an increased risk of mortality among those with low-SES characteristics (aHR:1.12; 95% CI:1.03-1.22) and mid-SES groups (aHR: 1.13; 95% CI:1.05-1.21). CONCLUSIONS: Among women with advanced-stage ovarian cancer who received systemic therapy, NH-Black women experienced poorer survival compared to NH-White women. Future studies should be directed to identify drivers of ovarian cancer disparities, particularly racial differences in treatment response and surveillance.

Infiltrative pattern of invasion is independently associated with shorter survival and desmoplastic stroma markers FAP and THBS2 in mucinous ovarian carcinoma.

AIMS: Mucinous ovarian carcinoma (MOC) is a rare ovarian cancer histotype with generally good prognosis when diagnosed at an early stage. However, MOC with the infiltrative pattern of invasion has a worse prognosis, although to date studies have not been large enough to control for covariables. Data on reproducibility of classifying the invasion pattern are limited, as are molecular correlates for infiltrative invasion. We hypothesized that the invasion pattern would be associated with an aberrant tumour microenvironment. METHODS AND RESULTS: Four subspecialty pathologists assessed interobserver reproducibility of the pattern of invasion in 134 MOC. Immunohistochemistry on fibroblast activation protein (FAP) and THBS2 was performed on 98 cases. Association with survival was tested using Cox regression. The average interobserver agreement for the infiltrative pattern was moderate (kappa 0.60, agreement 86.3%). After reproducibility review, 24/134 MOC (18%) were determined to have the infiltrative pattern and this was associated with a higher risk of death, independent of FIGO stage, grade, and patient age in a time-dependent manner (hazard ratio [HR] = 10.2, 95% confidence interval [CI] 3.0-34.5). High stromal expression of FAP and THBS2 was more common in infiltrative MOC (FAP: 60%, THBS2: 58%, both P < 0.001) and associated with survival (multivariate HR for FAP: 1.5 [95% CI 1.1-2.1] and THBS2: 1.91 [95% CI 1.1-3.2]). CONCLUSIONS: The pattern of invasion should be included in reporting for MOC due to the strong prognostic implications. We highlight the histological features that should be considered to improve reproducibility. FAP and THBS2 are associated with infiltrative invasion in MOC.

Trends in Location of Death for Individuals With Ovarian Cancer in the United States.

Using the publicly available Centers for Disease Control and Prevention's WONDER (Wide-ranging Online Data for Epidemiologic Research) database from 2003 to 2019, we evaluated associations between decedent characteristics and location of death for patients with ovarian malignancy. We found that Black, Native American, Asian American, and Hispanic patients were more likely to die in hospitals than White patients, despite an overall reduction in hospital deaths and an overall increase in hospice facility deaths. Additionally, patients with lesser educational attainment were more likely to die in nursing facilities and less likely to die in hospice facilities. Although there may be some contribution from cultural preferences, these findings may represent disparities in access to palliative care affecting people with cancer from racial and ethnic minoritized groups.

Deprivation and segregation in ovarian cancer survival among African American women: a mediation analysis.

PURPOSE: Deprivation and segregation indices are often examined as possible explanations for observed health disparities in population-based studies. In this study, we assessed the role of recognized deprivation and segregation indices specifically as they affect survival in a cohort of self-identified Black women diagnosed with ovarian cancer who enrolled in the African American Cancer Epidemiology Study. METHODS: Mediation analysis was used to examine the direct and indirect effects between deprivation or segregation and overall survival via a Bayesian structural equation model with Gibbs variable selection. RESULTS: The results suggest that high socioeconomic status-related indices have an association with increased survival, ranging from 25% to 56%. In contrast, index of concentration at the extremes-race does not have a significant impact on overall survival. In many cases, the indirect effects have very wide credible intervals; consequently, the total effect is not well estimated despite the estimation of the direct effect. CONCLUSIONS: Our results show that Black women living in higher socioeconomic status neighborhoods are associated with increased survival with ovarian cancer using area-level economic indices such as Yost or index of concentration at the extremes-income. In addition, the Kolak urbanization index has a similar impact and highlights the importance of area-level deprivation and segregation as potentially modifiable social factors in ovarian cancer survival.

Trends in incidence and mortality for ovarian cancer in China from 1990 to 2019 and its forecasted levels in 30 years.

BACKGROUND: The specific long-term trend in ovarian cancer (OC) rates in China has been rarely investigated. We aimed to estimate the temporal trends in incidence and mortality rates from 1990 to 2019 in OC and predict the next 30-year levels. Data on the incidence, mortality rates, and the number of new cases and deaths cases due to OC in the China cohort from 1990 to 2019 were retrieved from the Global Burden of Disease Study 2019. Temporal trends in incidence and mortality rates were evaluated by joinpoint regression models. The incidence and mortality rates and the estimated number of cases from 2020 to 2049 were predicted using the Bayesian age-period-cohort model. RESULTS: Consecutive increasing trends in age-standardized incidence (average annual percent change [AAPC] = 2.03; 95% confidence interval [CI], 1.90-2.16; p < 0.001) and mortality (AAPC = 1.58; 95% CI, 1.38-1.78; p < 0.001) rates in OC were observed from 1990-2019 in China. Theoretically, both the estimated age-standardized (per 100,000 women) incidence (from 4.77 in 2019 to 8.95 in 2049) and mortality (from 2.88 in 2019 to 4.03 in 2049) rates will continue to increase substantially in the coming 30 years. And the estimated number of new cases of, and deaths from OC will increase by more than 3 times between 2019 and 2049. CONCLUSIONS: The disease burden of OC in incidence and mortality has been increasing in China over the past 30 years and will be predicted to increase continuously in the coming three decades.

Disparities in refusal of surgery for gynecologic cancer.

OBJECTIVE: To identify sociodemographic and clinical factors associated with refusal of gynecologic cancer surgery and to estimate its effect on overall survival. METHODS: The National Cancer Database was surveyed for patients with uterine, cervical or ovarian/fallopian tube/primary peritoneal cancer treated between 2004 and 2017. Univariate and multivariate logistic regression were used to assess associations between clinico-demographic variables and refusal of surgery. Overall survival was estimated using the Kaplan-Meier method. Trends in refusal over time were evaluated using joinpoint regression. RESULTS: Of 788,164 women included in our analysis, 5875 (0.75%) patients refused surgery recommended by their treating oncologist. Patients who refused surgery were older at diagnosis (72.4 vs 60.3 years, p < 0.001) and more likely Black (OR 1.77 95% CI 1.62-1.92). Refusal of surgery was associated with uninsured status (OR 2.94 95% CI 2.49-3.46), Medicaid coverage (OR 2.79 95% CI 2.46-3.18), low regional high school graduation (OR 1.18 95% CI 1.05-1.33) and treatment at a community hospital (OR 1.59 95% CI 1.42-1.78). Patients who refused surgery had lower median overall survival (1.0 vs 14.0 years, p < 0.01) and this difference persisted across disease sites. Between 2008 and 2017, there was a significant increase in refusal of surgery annually (annual percent change +1.41%, p < 0.05). CONCLUSIONS: Multiple social determinants of health are independently associated with refusal of surgery for gynecologic cancer. Given that patients who refuse surgery are more likely from vulnerable, underserved populations and have inferior survival, refusal of surgery should be considered a surgical healthcare disparity and tackled as such.

Clinical Activity of Olvimulogene Nanivacirepvec-Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer: The Nonrandomized Phase 2 VIRO-15 Clinical Trial.

Importance: Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need. Objective: To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC. Design, Setting, and Participants: This open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022. Interventions: Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab. Main Outcomes and Measures: Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS). Results: Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths. Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02759588.

A retrospective analysis of secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in patients with recurrent ovarian cancer.

AIM: To evaluate the effect of secondary cytoreductive surgery (SeCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer patients. METHODS: This retrospective study analyzed a prospective database. We collected information of 389 patients who were diagnosed with recurrent epithelial ovarian cancer. All patients underwent SeCRS with or without HIPEC. Overall survival and progression-free survival (PFS) were used to evaluate the treatment effectiveness. RESULTS: Of the 389 patients collected, 123 underwent primary or interval cytoreductive surgery at initial treatment and SeCRS at recurrence (Group A), 130 underwent primary or interval cytoreductive surgery at initial and SeCRS plus HIPEC at recurrence (Group B), and 136 underwent primary or interval cytoreductive surgery plus HIPEC at initial and SeCRS plus HIPEC at recurrence (Group C). The median overall survival for Groups A, B, and C were 49.1 months (95% confidence interval [CI]: 47.6-50.5), 56.0 months (95% CI: 54.2-57.7), and 64.4 months (95% CI: 63.1-65.6), respectively. The median PFS for Groups A, B, and C were 13.1 months (95% CI: 12.6-13.5), 15.0 months (95% CI: 14.2-15.7), and 16.8 months (95% CI: 16.1-17.4), respectively. There were no significant difference in incidence and grade of adverse events among groups. CONCLUSIONS: This study suggested that SeCRS plus HIPEC followed by chemotherapy resulted in longer overall survival and PFS than only SeCRS followed by chemotherapy in patients with recurrent ovarian cancer, especially in patients who were treated with repeat HIPEC.

Health-care access dimensions and ovarian cancer survival: SEER-Medicare analysis of the ORCHiD study.

BACKGROUND: Racial and ethnic disparities in ovarian cancer (OC) survival are well-documented. However, few studies have investigated how health-care access (HCA) contributes to these disparities. METHODS: To evaluate the influence of HCA on OC mortality, we analyzed 2008-2015 Surveillance, Epidemiology, and End Results-Medicare data. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HCA dimensions (affordability, availability, accessibility) and OC-specific and all-cause mortality, adjusting for patient characteristics and treatment receipt. RESULTS: The study cohort included 7590 OC patients: 454 (6.0%) Hispanic, 501 (6.6%) Non-Hispanic (NH) Black, and 6635 (87.4%) NH White. Higher affordability (HR = 0.90, 95% CI = 0.87 to 0.94), availability (HR = 0.95, 95% CI = 0.92 to 0.99), and accessibility scores (HR = 0.93, 95% CI = 0.87 to 0.99) were associated with lower risk of OC mortality after adjusting for demographic and clinical factors. Racial disparities were observed after additional adjustment for these HCA dimensions: NH Black patients experienced a 26% higher risk of OC mortality compared with NH White patients (HR = 1.26, 95% CI = 1.11 to 1.43) and a 45% higher risk among patients who survived at least 12 months (HR = 1.45, 95% CI = 1.16 to 1.81). CONCLUSIONS: HCA dimensions are statistically significantly associated with mortality after OC and explain some, but not all, of the observed racial disparity in survival of patients with OC. Although equalizing access to quality health care remains critical, research on other HCA dimensions is needed to determine additional factors contributing to disparate OC outcomes by race and ethnicity and advance the field toward health equity.

Purine Intake and All-Cause Mortality in Ovarian Cancer: Results from a Prospective Cohort Study.

BACKGROUND: Current biological evidence suggests that purine involvement in purine metabolism may contribute to the development and progression of ovarian cancer (OC), but the epidemiological association is currently unknown. METHODS: A total of 703 newly diagnosed patients with OC aged 18-79 years were included in this prospective cohort study. Utilizing a verified food-frequency questionnaire, the participants' dietary consumption was gathered. Using medical records and ongoing follow-up, the deaths up until 31 March 2021 were determined. To assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of purine intake with OC mortality, Cox proportional-hazard models were utilized. RESULTS: During the median follow-up of 31 months (interquartile: 20-47 months), 130 deaths occurred. We observed an improved survival for the highest tercile of total purine intake compared with the lowest tercile (HR = 0.39, 95% CI = 0.19-0.80; p trend < 0.05), and this protective association was mainly attributed to xanthine intake (HR = 0.52, 95% CI = 0.29-0.94, p trend < 0.05). Additionally, we observed a curving relationship in which OC mortality decreased with total purine intake, and the magnitude of the decrease was negatively correlated with intake (p non-linear < 0.05). Significant inverse associations were also observed in subgroup analyses and sensitivity analyses according to demographic and clinical characteristics. Moreover, we observed that xanthine intake and hypoxanthine intake had a multiplicative interaction with ER and PR expression (p < 0.05), respectively. CONCLUSION: A high total purine and xanthine intake was linked to a lower risk of OC mortality. Further clarification of these findings is warranted.

Nomograms to predict the prognosis in malignant ovarian germ cell tumors: a large cohort study.

BACKGROUND: Malignant ovarian germ cell tumors (MOGCTs) are rare gynecologic neoplasms. The use of nomograms that are based on various clinical indicators to predict the prognosis of MOGCTs are currently lacking. METHODS: Clinical and demographic information of patients with MOGCT recorded between 2004 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database, and Cox regression analysis was performed to screen for important independent prognostic factors. Prognostic factors were used to construct predictive calculational charts for 1-year, 3-year, and 5-year overall survival (OS). The externally validated case cohort included a total of 121 MOGCT patients whose data were recorded from 2008 to 2019 from the database of the Shengjing Hospital of China Medical University. RESULTS: A total of 1401 patients with MOGCT were recruited for the study. A nomogram was used to forecast the 1-year, 3-year, and 5-year OS using data pertaining to age, International Federation of Gynecology and Obstetrics (FIGO) staging, histological subtype and grade, and surgical type. Nomograms have a more accurate predictive ability and clinical utility than FIGO staging alone. Internal and external validation also demonstrated satisfactory consistency between projected and actual OS. CONCLUSIONS: A nomogram constructed using multiple clinical indicators provided a more accurate prognosis than FIGO staging alone. This nomogram may assist clinicians in identifying patients who are at increased risk, thus implementing individualized treatment regimens.

Identification of a novel gene signature predicting response to first-line chemotherapy in BRCA wild-type high-grade serous ovarian cancer patients.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) has poor survival rates due to a combination of diagnosis at advanced stage and disease recurrence as a result of chemotherapy resistance. In BRCA1 (Breast Cancer gene 1) - or BRCA2-wild type (BRCAwt) HGSOC patients, resistance and progressive disease occur earlier and more often than in mutated BRCA. Identification of biomarkers helpful in predicting response to first-line chemotherapy is a challenge to improve BRCAwt HGSOC management. METHODS: To identify a gene signature that can predict response to first-line chemotherapy, pre-treatment tumor biopsies from a restricted cohort of BRCAwt HGSOC patients were profiled by RNA sequencing (RNA-Seq) technology. Patients were sub-grouped according to platinum-free interval (PFI), into sensitive (PFI > 12 months) and resistant (PFI < 6 months). The gene panel identified by RNA-seq analysis was then tested by high-throughput quantitative real-time PCR (HT RT-qPCR) in a validation cohort, and statistical/bioinformatic methods were used to identify eligible markers and to explore the relevant pathway/gene network enrichments of the identified gene set. Finally, a panel of primary HGSOC cell lines was exploited to uncover cell-autonomous mechanisms of resistance. RESULTS: RNA-seq identified a 42-gene panel discriminating sensitive and resistant BRCAwt HGSOC patients and pathway analysis pointed to the immune system as a possible driver of chemotherapy response. From the extended cohort analysis of the 42 DEGs (differentially expressed genes), a statistical approach combined with the random forest classifier model generated a ten-gene signature predictive of response to first-line chemotherapy. The ten-gene signature included: CKB (Creatine kinase B), CTNNBL1 (Catenin, beta like 1), GNG11 (G protein subunit gamma 11), IGFBP7 (Insulin-like growth factor-binding protein 7), PLCG2 (Phospholipase C, gamma 2), RNF24 (Ring finger protein 24), SLC15A3 (Solute carrier family 15 member 3), TSPAN31 (Tetraspanin 31), TTI1 (TELO2 interacting protein 1) and UQCC1 (Ubiquinol-cytochrome c reductase complex assembly factor). Cytotoxicity assays, combined with gene-expression analysis in primary HGSOC cell lines, allowed to define CTNNBL1, RNF24, and TTI1 as cell-autonomous contributors to tumor resistance. CONCLUSIONS: Using machine-learning techniques we have identified a gene signature that could predict response to first-line chemotherapy in BRCAwt HGSOC patients, providing a useful tool towards personalized treatment modalities.

A prognostic model of patients with ovarian mucinous adenocarcinoma: a population-based analysis.

BACKGROUND: Ovarian mucinous carcinoma is a disease that requires unique treatment. But for a long time, guidelines for ovarian serous carcinoma have been used for the treatment of ovarian mucinous carcinoma. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with ovarian mucinous adenocarcinoma. METHODS: In this study, patients initially diagnosed with ovarian mucinous adenocarcinoma from 2004 to 2015 were screened from the Surveillance, Epidemiology, and End Results (SEER) database, and divided into the training group and the validation group at a ratio of 7:3. Independent risk factors for OS and CSS were determined by multivariate Cox regression analysis, and nomograms were constructed and validated. RESULTS: In this study, 1309 patients with ovarian mucinous adenocarcinoma were finally screened and randomly divided into 917 cases in the training group and 392 cases in the validation group according to a 7:3 ratio. Multivariate Cox regression analysis showed that the independent risk factors of OS were age, race, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. Independent risk factors of CSS were age, race, marital, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. According to the above results, the nomograms of OS and CSS in ovarian mucinous adenocarcinoma were constructed. In the training group, the C-index of the OS nomogram was 0.845 (95% CI: 0.821-0.869) and the C-index of the CSS nomogram was 0.862 (95%CI: 0.838-0.886). In the validation group, the C-index of the OS nomogram was 0.843 (95% CI: 0.810-0.876) and the C-index of the CSS nomogram was 0.841 (95%CI: 0.806-0.876). The calibration curve showed the consistency between the predicted results and the actual results, indicating the high accuracy of the nomogram. CONCLUSION: The nomogram provides 3-year and 5-year OS and CSS predictions for patients with ovarian mucinous adenocarcinoma, which helps clinicians predict the prognosis of patients and formulate appropriate treatment plans.

High expression of TRIM24 predicts worse prognosis and promotes proliferation and metastasis of epithelial ovarian cancer.

BACKGROUND: Tripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family. TRIM24 is claimed aberrantly activated in a number of cancers, such as breast cancer, prostate cancer and lung cancer. However, the expression of TRIM24 in epithelial ovarian cancer (EOC) and its relationship with prognosis remain unclear. In this study, we investigated the expression pattern and underlying clinical significance of TRIM24 in EOC. RESULTS: Data from Oncomine and immunohistochemistry of tissue samples demonstrated that TRIM24 expression was obviously elevated in ovarian carcinoma compared with normal ovary tissues. Elevated TRIM24 expression was closely correlated with serum CA-125 (P = 0.0294), metastasis (P = 0.0022), FIGO (International Federation of Gynecology and Obstetrics) stage (P = 0.0068) and Ki-67 level (P = 0.0395). Kaplan-Meier survival analysis found that TRIM24 expression increased inversely with the clinical prognosis of patients with EOC. Moreover, colony formation and CCK-8 assays showed that TRIM24 promoted EOC cell growth, and tumorigenic experiments in nude mice showed that TRIM24 knockdown inhibited tumor growth in vivo. The Spearman's correlations revealed that the expression of TRIM24 was significantly correlated with levels of Ki-67 (P = 0.01), at a correlation coefficient of 0.517. Wound-healing and transwell migration assays demonstrated TRIM24 facilitated cell migration. Mechanism studies showed that TRIM24 could promote the phosphorylation level of Akt and the process of EMT. CONCLUSION: Our results confirmed that TRIM24 could predict poor prognosis of EOC patients and promote tumor progression by regulating Akt pathway and EMT. TRIM24 may be used as a new prognostic marker for EOC and may provide a new strategy for targeted therapy of epithelial ovarian cancer.

Overexpression of Stathmin 1 Predicts Poor Prognosis and Promotes Cancer Cell Proliferation and Migration in Ovarian Cancer.

PURPOSE: The aim of this study was to investigate the expression of stathmin 1 (STMN1) in ovarian cancer and its effect on prognosis. The effect and mechanism of STMN1 on the proliferation and migration of ovarian cancer cells were also investigated. METHODS: Expression of STMN1 was measured by immunohistochemical staining in ovarian cancer tissues. The effects of STMN1 on the proliferation and migration capacity of ovarian cancer were evaluated using Cell Counting Kit-8 (CCK-8) assays, colony formation assays, immunofluorescence staining, wound healing assays, and Transwell assays. Transcription factors were predicted by bioinformatic analysis of TCGA database. RESULTS: STMN1 was upregulated in ovarian cancer tissues as compared to paracancerous tissues and associated with shorter overall survival. STMN1 expression significantly correlated with FIGO staging and tumor differentiation (P < 0.05). Furthermore, STMN1 promoted proliferation and migration in ovarian cancer cell lines. Bioinformatic analysis revealed that STMN1 was potentially regulated by E2F transcription factors. Then, we found that E2F1 regulated the expression of STMN1 and affected proliferation. CONCLUSION: STMN1 is overexpressed in ovarian cancer, and its high expression suggests a poor prognosis. STMN1 promotes the proliferation and migration of ovarian cancer and is regulated by E2F1. Thus, STMN1 may serve as a negative prognostic factor and possible target for the treatment of ovarian cancer patients.

Overexpression of CAPG Is Associated with Poor Prognosis and Immunosuppressive Cell Infiltration in Ovarian Cancer.

Historically, immunotherapies have only resulted in a partial response from patients with advanced ovarian cancer, resulting in poor clinical efficacy. A full understanding of immune-related gene expression and immunocyte infiltration in ovarian cancer would be instrumental for the improved implementation of immunotherapy. The Capping Actin Protein, Gelsolin-Like (CAPG) gene encodes an actin-regulatory protein, which plays important roles in tumor progression and immune regulation. This study is aimed at identifying the potential therapeutic and prognostic roles of CAPG in ovarian cancer. CAPG expression and clinical information were investigated in the data collected from TCGA, Oncomine, GEPIA, UALCAN, and Kaplan-Meier plotter. CAPG coexpression networks were evaluated by LinkedOmics, GeneMANIA, and NetworkAnalyst. The correlation of CAPG with immune infiltrates was analyzed via TIMER, ImmuCellAI, and GEPIA. Our result showed that patients with high tumoral CAPG expression had significantly shorter 5-year overall survival. Functional enrichment analysis indicated that CAPG-related phenotypes were largely involved in inflammatory response, chemokine and cytokine signaling, cell adhesion, and Toll-like receptor signaling pathways. CAPG expression was positively correlated with infiltrating levels of regulatory T cells (Tregs), tumor-associated macrophages (TAMs), and exhausted T cells (Texs) while being negatively correlated with infiltrating levels of natural killer T cells (NKTs) and neutrophils in ovarian cancer. Moreover, the expression of FOXP3, CD25, CD127, CCR8, and TGFß in respect to Tregs; CCL2 and CD68 in respect to TAM; CD163, VSIG4, and MS4A4A in respect to M2 macrophages; CD33 and CD11b in respect to myeloid-derived suppressor cells (MDSCs); and PD1, CTLA4, LAG3, TIM3, GZMB, 2B4, and TIGIT in respect to Texs was significantly correlated with CAPG expression in ovarian cancer. These findings suggest that CAPG may contribute to the immunosuppressive tumor microenvironment in ovarian cancer, leading to an exhausted T cell phenotype and tumor progression. Therefore, CAPG can be used as a potential biomarker for determining prognosis and immunotherapy effectiveness in ovarian cancer.

Association between pre-diagnostic dietary pattern and survival of ovarian cancer: Evidence from a prospective cohort study.

BACKGROUND: Evidence for a role of single nutrition or foods on ovarian cancer (OC) survival has been limited and inconclusive. Due to the potentially complex interactions in dietary, we applied dietary patterns to this study to firstly explore the relationship between the pre-diagnosis overall diet and OC survival. METHODS: The prospective cohort study was conducted among 853 OC patients aged 18-79 years during 2015-2020. Dietary intake was collected using a validated 111-item food frequency questionnaire. Deaths were obtained by medical records and cancer registry up to March 31, 2021. Cox proportional hazards regression models was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of pre-diagnosis dietary patterns with overall survival (OS). RESULTS: Overall, during the follow-up period (median: 37.57 months, interquartile: 25.00-50.17 months), 130 (18.49%) OC patients died. Four dietary patterns were identified: healthy pattern, ethnic pattern, animal foods pattern, and sweet pattern. The highest tertile of the healthy pattern scores was related to better OS compared with the lowest tertile scores (HR = 0.54, 95% CI = 0.30-0.98, p trend <0.05), whereas OC patients with highest adherence to the animal foods pattern was associated with worse OS than those with the lowest adherence (HR = 1.90, 95% CI = 1.14-3.17, p trend <0.05). We found no significant associations between adherence to ethnic pattern and sweet pattern and OS of OC patients. CONCLUSION: Pre-diagnosis healthy patterns was associated with better OC survival, whereas animal pattern was associated with worse survival among OC survivals.