bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening mitophagy-related lncRNAs based on WGCNA to identify and validate a prognostic signature for patients with ovarian cancer.
Authors: Zheng Jianfeng , Sun Yang 
Published: June 2023

e17554 Background: Mitophagy refers to the process by which cells selectively remove incomplete or damaged mitochondria through the autophagic mechanism. However, the value of mitophagy-related genes (MRGs) and mitophagy-related lncRNAs (MRLs) in ovarian cancer (OC) is still not clear. Methods: We explored the alterations of MRGs in four gynecological tumors using R packages. Based on weighted coexpression network analysis (WGCNA), MRLs were identified to carry out LASSO Cox regression analysis and then we established the prognostic MRL-signature. The prognosis and independent prognostic value of the MRL-signature was also validated by four independent datasets from GEO. The expression level of MRLs involved in the prognostic signature we established were detected by qPCR for the samples we collected. Analysis for characteristics of functional pathways, immunity status, and anti-tumor therapy were based on GSEA, ssGSEA, CIBERSORT, xCELL, MCPcounter, ESTIMATE, and TIDE. The ceRNA network was constructed applying miranda, miRWalk3.0, and Cytoscape. Results: Most MRGs were found at lower expression levels in four gynecological tumors. Among the four gynecological tumors, the levels of CNV and MRGs were positively correlated. Most MRGs were negatively correlated with methylation level. A total of 52 MRGs were differentially expressed in OC tissues. Nine MRLs were significantly associated with survival prognosis. Eight optimal lncRNA combinations were screened by LASSO Cox Regression algorithm. On the basis of Univariate Cox regression and Multivariate Cox regression analyses, the risk model based on MRLs was proved to be the independent prognostic factors. The qPCR assay showed that the differential expression trends of these MRLs in our collected OC samples were consistent with those in TCGA database. We found that TIDE score of OC patients with lower risk score was lower, suggesting that OC patients with low RSs are more sensitive to immune checkpoint blockade therapy. OC patients with higher risk score had higher immune cell scores and higher risk score correlated strongly with higher stromal and estimated scores, while lower risk score correlated with tumor purity. We found that the IC50 levels of paclitaxel and ABT.888 (Veliparib) in the high-risk group were observably higher than those in the low-risk group, suggesting a negative correlation between risk score and the drug susceptibility of OC. There were 539 miRNAs, 73 mRNAs and 8 lncRNAs in the ceRNA network. Conclusions: The integrative analysis of MRGs and MRLs revealed their roles in prognosis and therapeutic responsibility in chemotherapy and immunotherapy. Our findings demonstrate the important clinical significance of the signature based on MRLs, and will help improve clinical outcomes for patients with OC.
The peripheral TCR repertoire diversity indexes can be used as an independent indicator for long term survival rate of ovarian cancer patients.
Authors: Fu Kaiyu , Yang Xin , Li Kemin , Yin Rutie 
Published: June 2023

e17558 Background: According to GLOBOCAN 2020 data, ovarian cancer (OC) ranks 19th in incidence and 15th in mortality with a rate of 1.6% and 2.1%, respectively, High-grade serous OC is the most common sub-type of malignant ovarian tumors, remains the leading cause of cancer-related death among all gynecological cancers in the developed parts of the world. In the United States in 2016, 5-year survival rate was only 10-25% in stage III or IV OC patients, and there was considerable variability in survival in an advanced stage. At present, there is no reliable molecular marker to identify patients with better or worse prognosis. As is known to all, the adaptive immune system defends the body against different foreign antigens, using two main types of antigen receptors: T-cell receptors (TCRs) and antibodies. Now we use high-throughput sequencing approach to analyze the expressed TCRβ repertoires in the peripheral blood of OC patients and healthy women donors. Methods: The experimental design and participant recruitment were approved by Medical Ethics Committee of West China Second University Hospital (Ethics Approval for Research: 2022). Total RNA was extracted from PBMC using TRIZOL reagent. High through put sequencing of the TCRβ gene, assignment of the Vβ, Dβ, and Jβ germline gene, and TCR diversity indexes analyses were conducted essentially following our previously published protocols. Statistical analysis and graph drawing were performed using R language (R 4.0.3). Results: Comparison of the TCR repertoires between the 232 OC patients (OC group) and the 250 healthy women donors (HD group) revealed significant differences. For examples, the VJ combinations of the OC group were distinct from those of the HD group. In addition, the TCR repertoire diversity indexes of the OC group were significantly lower than those of the HD group ( p < 0.001), including D50s, Simpson indexes, the number of highly expressed clones (HECs), and the frequencies of the largest TCR clones. As reported before, the TCR repertoire diversity indexes decreased gradually with increasing age in the HD group (all p < 0.001). Moreover, the TCR repertoire diversities in the survival group were significantly higher than those in the death group (D50: p = 0.0342; the number of HECs: p = 0.0414). Using as the cut off value, the OC patients with D50 < 0.032 had significantly higher mortality rates compared to the OC patients with D50 > 0.032 ( p = 0.0019). Similarly, using the numbers of HECs or the frequencies of the largest TCR clones can also distinguish OC patients in long term survival. Conclusions: Analyzing the peripheral TCR repertoires in the OC and HD revealed significant differences, and the peripheral TCR repertoire diversity indexes may be used as a potential predictor for long term survival for ovarian cancer.
Is laparoscopic approach feasible in early-stage ovarian cancer? A retrospective study in single tertiary center.
Authors: Chang Chen Bin 
Published: June 2023

e17560 Background: Laparoscopic approach for early-stage ovarian cancer is a controversy. Current studies showed no negative impacts on these patients. However, some limitations were noted, such as small case numbers, heterogeneity, and retrospective study. Methods: We retrospectively reviewed our cases who was diagnosed as early-stage ovarian cancer and received staging surgery from 2009 through 2017. There patients were divided into two groups, via laparoscopic staging or laparotomy. The primary outcome was progression-free survival. The secondary outcomes were overall survival and intra-operative rupture rate. We performed the Kaplan-Meier method and chi-square test for analyzing survival outcome and factors, in order to evaluate impacts on different surgical methods. Results: Total 520 patients (2014 FIGO stage IA-IC3) were enrolled, including 355 patients who underwent open surgery and 165 patients who underwent laparoscopic surgery. The median follow-up time for survivors was 71(range,39.7-102.3）months. The progression-free survival was similar between two groups and all subgroups. The overall survival was also similar between two surgical methods and all subgroups, except subgroup of clear cell carcinoma. The p-value of overall survival in clear cell carcinoma patients was 0.05. However, the case numbers of clear cell carcinoma 81 in laparotomy group and 31 in laparoscopy group, respectively. The intra-operative rupture rate was increased in laparoscopic group. The relative risk and p-value were 1.139 and 0.043, respectively. Conclusions: Laparoscopic may be feasible in early-stage ovarian cancer in selected patients and expert surgeon due to higher intra-operative rupture rate. If clear cell carcinoma of ovary was highly suspected, the surgeon should be alerted because poorer overall survival in clear cell carcinoma of ovary patients was observed.
Can epigenetic treatments efficiently revoke the ability of 3D ovarian cancer cells to proliferate, migrate, and invade?
Authors: Kelly Rebeca , Aviles Diego , Warshal David Philip , Krill Lauren , Ostrovsky Olga 
Published: June 2023

e17562 Background: 3D ovarian cancer propagation and metastasis arise not only from genetic mutations, but from aberrant epigenetic modifications known to involve mechanisms of DNA methylation and histone deacetylation. Clinically, cancer induces epigenetic aberrations in adipose-derived stem cells from omentum (O-ASCs), creating a tumorigenic microenvironment that supports chemoresistance and dissemination of disease. Epigallocatechin gallate (EGCG), a DNA methyltransferase inhibitor derived from green tea, and Indole-3-carbinol (I3C), a histone deacetylase inhibitor from cruciferous vegetables, carry promising effects in reprograming aberrant epigenetic modifications in cancer. Therefore, we investigate whether these diet-derived compounds can suppress proliferation, migration and invasion of ovarian cancer in 3D-spheroids or 3D-organoids with O-ASCs when compared to synthetic Panobinostat (Pano) and cisplatin/paclitaxol (C/T). Methods: 3D ovarian cancer spheroids and organoids (30% O-ASCs) were treated with EGCG (10, 50 µm), I3C (50, 200 µm), Pano (5, 15 µm) and C/T. Percent growth was followed for 17 days and compared to an untreated control group. Post-treated cancer was then derived from 3D structures and tested for its ability to regrow (MTT assay), to form colonies (CFU), and to migrate and invade (CytoSelect Cell Migration and Invasion assay). Results: Our results show that higher doses of epigenetic regimens more efficiently suppress growth of 3D ovarian cancer when compared to the control and C/T groups (p<.05). Additionally, the synthetic epigenetic drug Pano also efficiently suppressed cancer as compared to control and C/T treated cells (p<.05). Given that experimental treatments efficiently down-regulated 3D cancer growth, follow up of post-treatment cancer recovery was analyzed through multiple biochemical and biological assays. 3D derived cells pre-treated with EGCG, I3C and Pano had significant lower proliferation capacity as compared to control or C/T as demonstrated by an MTT assay (p<.05). While all epigenetic treatments inhibited CFU in the spheroid derived group, EGCG was not able to fully inhibit CFU in the organoid group. Further, inhibition of CFU was not noted in the C/T pre-treated cells. Finally, the ability of cells to migrate and invade following treatment was more efficiently suppressed in cells derived from organoids. I3C and Pano significantly suppressed cancer migration, while EGCG and Pano suppressed invasion (p<.05). Conclusions: Diet-derived epigenetic treatments can reprogram epigenetic aberrations involved in mechanisms of proliferation, migration and invasion of 3D ovarian cancer. Our results suggest that these treatments not only suppress 3D cancer growth and post-treatment regrowth, but could be considered as adjuncts to standard chemotherapy, improving efficiency and patient outcomes.
Genetic counseling and testing for epithelial ovarian cancer in a diverse patient population.
Authors: Kim Kee-Hwan Michael , Hayek Judy , Acker Cheyenne , An Anjile , Zhang Peilin , Gorelick Constantine , Kanis Margaux Jenna 
Published: June 2023

e17563 Background: According to the current American Society of Clinical Oncology (ASCO) guidelines, “all women diagnosed with epithelial ovarian cancer should be offered germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes, irrespective of their clinical features or family history”. Test results have implications for surveillance, familial testing, and treatment. We investigated how genetic counseling and testing rates at a New York City tertiary care center with a large minority population compared with national rates, and if any disparities existed. Methods: This is a retrospective cohort study of patients with newly diagnosed epithelial ovarian, fallopian tube, peritoneal cancer between January 2014 and June 2022. Data were obtained from pathology and chemotherapy databases at the NewYork-Presbyterian Brooklyn Methodist Hospital. Variables including age, race, ethnicity, BMI, insurance, language, family history of cancer, date of diagnosis, stage, and genetic counseling/testing status were manually extracted. Descriptive statistics were used to characterize the variables of interest. Chi-square/Fisher’s exact tests were used to examine the association between genetic counseling/testing and categorical variables. Wilcoxon rank-sum/t-tests were used for association between continuous factors. The Mann-Kendall trend test was used to assess year-to-year trends. Results: 144 patients were identified. Mean age at diagnosis was 63 years (SD:13). This diverse cohort included 51% white, 36% black, 3.5% Asian, 9% other/unknown; 9% were of Hispanic ethnicity and 26% were non-English speaking. 104 (72%) patients received genetic counseling and 99 (69%) received subsequent genetic testing. 95% of those that underwent genetic counseling underwent subsequent testing. The genetic counseling and testing rates were not influenced by race, ethnicity, language, insurance type, BMI, family history of cancer. It was associated with significant difference by cancer stage (p < 0.01). There was a significant upward trend of proportion of patients that received genetic counseling from 47% in 2015 to 100% in 2022 (p < 0.01). Most genetic counseling was performed by a gynecologic oncologist (93%) as opposed to a genetic counselor (6.7%). Overall, 12 (8.3%) patients were BRCA+. Conclusions: Genetic counseling and testing rates within this diverse study population proved to be at least twice as high as the national average of 10-30%, with an increasing year-to-year trend. There were no disparities observed, in contrast to previously published data. BRCA mutation detection was in line with established prevalence within ovarian cancer, indicating adequate screening. Concentrated efforts on behalf of oncologists ensures excellent access to testing.
Comparison of BRCA genetic testing and subsequent treatment with PARP inhibitors (PARPi) for ederly vs non-elderly women with non-mucinous epithelial ovarian cancer (EOC): A large prospective cohort study from the Australian National Gynaecology Oncology Registry (NGOR).
Authors: Naidoo Mahendra , Scott Clare L. , McNally Orla , Rome Rob , Perera Sharnel , Zalcberg John Raymond 
Published: June 2023

e17566 Background: The 5-year survival rate for elderly women (≥ 75 years) with ovarian cancer is 25%. Germline mutations in BRCA1/BRCA2 are identified in approximately 15% of newly diagnosed women with ovarian cancer and have implications for prognosis and predicted benefit of both platinum chemotherapy and PARPi therapy. Objectives: To compare differences in, and subsequent management of Elderly (aged ≥75 years) vs Non-elderly (aged <75 years) women with non-mucinous EOC who underwent germline and somatic BRCA1/BRCA2 testing across the Australian NGOR sites from 2017 – 2022. Methods: Clinical data were sourced from NGOR patient databases and assessed to confirm accuracy prior to analysis. Results: Data on 1579 eligible women between May 2017 and July 2022 across 21 hospitals were collected. Patient characteristics are summarised in Table 1. The rates of germline testing in Elderly women was 51% compared to 71% in Non-elderly women and this difference was statistically significant (p<0.001). The rates of somatic testing in Elderly women was 28% compared to 33% in Non-elderly women although this difference was not statistically significant (p=0.2). In Elderly women with either germline or somatic pathogenic BRCA mutations and Stage III/IV disease, 67% received PARPi within 8 weeks of chemotherapy completion compared to 53% in Non-elderly women. In a multi-variate analysis, the most significant characteristic associated with reduced germline testing was the ‘Elderly’ compared to ‘Non-elderly’ group (OR 0.41, 95% CI: 0.30-0.58, p < 0.001). Germline testing was more likely to be conducted in postcodes associated with higher Socioeconomic status (SES) quintiles 2-5 compared to quintile 1 (OR 2.06, 95% CI: 1.50-2.81, p< 0.001) and in those women receiving operative and chemotherapy treatment compared to chemotherapy alone (OR 1.84, 95% CI: 1.08-3.11, p=0.024). Conclusions: The rates of germline and somatic BRCA testing are lower than anticipated, particularly germline testing in Elderly women. Women known to have pathogenic germline or somatic BRCA mutations may have received PARPi at lower rates than expected. Further studies are required to understand the cause of such variations, including accounting for the advent of government funded BRCA testing, PARPi funding and correlating effects on survival. [Table: see text]
Demographic and socioeconomic factors in poorly differentiated Sertoli-Leydig cell tumors: A National Cancer Database analysis.
Authors: Cogua Laura 
Published: June 2023

e17568 Background: Poorly differentiated Sertoli-Leydig cell tumor (PD-SLCT) is a rare and aggressive type of ovarian cancer. This cancer has a 5-year cancer-specific survival rate of 43.9% with a chance of early relapse of approximately 2-3 years following initial diagnosis. Given the rarity of the cancer, potential risk factors could offer providers and patients more information about the epidemiology. The National Cancer Database (NCDB) was analyzed to study the demographic factors in patients diagnosed with PD-SLCT. Methods: Cases of PD-SLCT (N = 405) in the NCDB from 2004 – 2020 were determined via histology (ICD-O-3 code = 8631). A retrospective cohort analysis using demographic factors such as race, age, sex, insurance status, urban/rural, facility type, and Charleson-Deyo score were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: A total of 405 patients with a diagnosis of PD-SLCT were identified in the database with a steady incidence of patients diagnosed per year (mean = 23.8 per year, R2 = 0.1). The average age of diagnosis was 41.7 years (SD = 20.1, range = 8 – 90 years). The majority of patients were non-Hispanic (82.5%) and White (69.4 %). More patients were in the top quartile of income earners (30.8.%) and were privately insured (56.8%) relative to those who were uninsured or insured by Medicare/Medicaid (43.2%). A greater percentage of patients with PD-SLCT were treated at a non-academic program (54.0%) compared to an academic/research program (46.0%). More patients lived in metropolitan counties with a population greater than 1 million (59.8%) versus less populated metropolitan communities or urban communities (40.2%). Most individuals (84.2%) had Charlson-Deyo comorbidity scores of 0. Conclusions: This novel study of the NCDB addresses a significant knowledge gap on patients with PD-SLCT, as it provides demographic insight into this rare type of tumor and the patients who are diagnosed with it. Most PD-SLCT patients tend to be in the premenopausal age, as previously described in literature. Most patients are White and non-Hispanic. This is the first time the socioeconomic factors of PD-SLCT patients have been described in the literature: patients are more likely to be in the top income quartile, live in densely populated metropolitan areas, and be treated in a non-academic program. Further research is needed to better understand the impact of these factors on the diagnosis of, treatments utilized, and overall survival of patients with PD-SLCT to ensure that all patients receive the best possible care, regardless of their background.
Prognostic risk stratification of low-grade serous ovarian cancer: Model development and validation based on machine learning algorithm.
Authors: Chen Zhongshao , Zhang Kai , Chu Ran , Song Kun 
Published: June 2023

e17569 Background: Low-grade serous ovarian cancer (LGSOC) is a rare ovarian tumor that lacks a prognostic prediction model. We attempted to construct a clinical nomogram to predict the recurrence and survival of patients with LGSOC. Methods: A multicenter clinical cohort of 199 patients with pathologically confirmed LGSOC was constructed. The predictive model factors were recurrence and survival related clinical factors, which were determined by univariate and multivariate COX regression analysis. The area under receiver operating characteristic curve (AUC), and calibration curve were used to assess the accuracy and discrimination of the nomogram. The concordance index(C-index), net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to evaluate the efficacy of nomogram and FIGO staging in predicting recurrence and survival. Results: A total of 155 patients were included, and four independent prognostic factors were identified to construct the prediction model. The AUC ( > 0.8) showed satisfactory discriminative ability of the nomogram, and the calibration curve showed good agreement between the predicted outcome and the actual outcome. The C-index (PFS: 0.791 vs 0.693; OS: 0.808 vs 0.674), NRI values (0.181 for 3-year and 0.278 for 5-year OS prediction) and IDI values(0.141 for 3-year and 0.147 for 5-year OS prediction, 0.089 for 3-year and 0.079 for 5-year PFS prediction) results showed that nomogram performed better than FIGO staging in predicting prognosis(p < 0.01). Conclusions: We constructed and validated clinical nomogram to individually predict recurrence and survival outcomes in patients with LGSOC, which can help evaluate the prognosis of patients.
The impact of lymphadenectomy on survival outcomes of ovarian clear cell carcinoma: A systematic review and meta-analysis.
Authors: Liu Yan , Song Kun , Huang Changzhen , Chu Ran 
Published: June 2023

e17572 Background: The treatment strategies for ovarian clear cell carcinoma (OCCC) are the same as those for epithelial ovarian cancer. Due to the rarity of OCCC, no prospective studies of its surgery have been reported. Therefore, the therapeutic significance of lymphadenectomy for OCCC needs to be further clarified. Methods: The Web of Science, Scopus, PubMed, and other sources (e.g. Google Scholar) were searched from each database’s earliest inception to June 2021. English-language publications of observational studies that investigated the role of lymphadenectomy in patients with OCCC were included.The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: The analysis demonstrated that lymphadenectomy is associated with significantly improved disease-specific survival (DSS) (HR = 0.76; 95%CI = 0.60-0.95; P = 0.02; I2= 0.0%) and disease-free survival (DFS) (HR = 0.58; 95%CI = 0.33-1.00; P = 0.05; I2= 61%), but not for overall survival (OS) (HR = 0.80; 95%CI = 0.60-1.06; P = 0.12; I2= 19%) and progression-free survival (PFS) (HR = 0.95; 95%CI = 0.64-1.42; P = 0.79; I2= 0.0%). But it is worth noting that several single studies indicated a tendency of improved OS, PFS, DFS, DSS with lymphadenectomy. The discrepancy of different results from similar studies should be viewed with caution. Conclusions: Lymphadenectomy could not significantly improve OS and PFS for OCCC, but is associated with improved DFS and DSS. Gynecologic oncologists should tailor treatment to patients to achieve optimal outcomes. Lymph node metastasis should be detected as accurately as possible before and during surgery to identify patients who can benefit from lymphadenectomy. The establishment of an international OCCC database and the development of multicenter clinical studies with international cooperation will help improve the treatment strategy.