scRNA-seq Can Identify Different Cell Populations in Ovarian Cancer Bulk RNA-seq Experiments.

High-grade serous ovarian cancer (HGSC) is a heterogeneous disease. RNA sequencing (RNAseq) of bulk solid tissue is of limited use in these populations due to heterogeneity. Single-cell RNA-seq (scRNA-seq) allows for the identification of diverse genetic compositions of heterogeneous cell populations.

A Natural Language Processing Method Identifies an Association Between Bacterial Communities in the Upper Genital Tract and Ovarian Cancer.

Bacterial communities within the female upper genital tract may influence the risk of ovarian cancer. In this retrospective cohort pilot study, we aim to detect different communities of bacteria between ovarian cancer and normal controls using topic modeling, a natural language processing tool. RNA was extracted and analyzed using the VITCOMIC2 pipeline.

Endometrial carcinosarcoma without myoinvasion.

Objective: Uterine carcinosarcoma without myoinvasion, limited to the endometrial lining/polyp or with no residual uterine disease at the time of hysterectomy, is extremely uncommon, with unknown oncologic outcomes. Thus, this study aimed to evaluate the long-term outcomes of patients with carcinosarcoma without myoinvasion.

Methods: Patients with International Federation of Gynecology and Obstetrics 2009 stage IA carcinosarcoma without myoinvasion who underwent surgery from December 1998 to January 2023 were identified from 11 centers worldwide.

Identifying ovarian cancer with machine learning DNA methylation pattern analysis.

The majority of patients with epithelial ovarian cancer (EOC) continue to be diagnosed at an advanced stage despite great advances in this disease treatment. To impact overall survival, we need better methods of EOC early diagnosis. We performed a case control study to predict high-grade serous cancer (HGSC) using artificial intelligence methodology and methylated DNA from surgical specimens.

Training, Validating, and Testing Machine Learning Prediction Models for Endometrial Cancer Recurrence.

Purpose: Endometrial cancer (EC) is the most common gynecologic cancer in the United States with rising incidence and mortality. Despite optimal treatment, 15%-20% of all patients will recur. To better select patients for adjuvant therapy, it is important to accurately predict patients at risk for recurrence.

ECPPF stratification identifies occult high-risk subgroups in stage I, grade 1 or 2, ≤50 % invasive endometrial cancer: Candidates for adjuvant therapy.

Objective: To determine whether stratification with ECPPF (E2F1 + CCNA2 log2 expression and POLE, PPP2R1A, and FBXW7 variants) could identify occult cases of high-risk endometrial cancer (EC) in a traditionally low-risk cohort.

Methods: We identified 97 cases of clinicopathologic low-risk endometrioid EC (defined as stage I, grade 1 or 2, limited [≤50 %] myometrial invasion) from The Cancer Genome Atlas (TCGA). Twelve cases had POLE mutations (mu) and 15 had PPP2R1Amu or FBXW7mu.

Gynecological Cancers Among American Indian and Alaska Native Women Living in the Upper Midwest, 1995-2019.

Background: American Indian and Alaska Native (AI/AN) women experience higher rates of mortality from many cancers than their non-Native counterparts.

Objective: To examine recent data on gynecological cancers (cervical, ovarian, and uterine) among AI/AN women living in the Upper Midwest (Iowa, Montana, Nebraska, North Dakota, South Dakota, and Wyoming) for any improvement in equity.

Methods: We used data from the North American Association for Central Cancer Registries Cancer in North America database (1995-2019).

Identification of Ovarian High-Grade Serous Carcinoma with Mitochondrial Gene Variation.

Women diagnosed with advanced-stage ovarian cancer have a much worse survival rate than women diagnosed with early-stage ovarian cancer, but the early detection of this disease remains a clinical challenge. Some recent reports indicate that genetic variations could be useful for the early detection of several malignancies. In this pilot observational retrospective study, we aimed to assess whether mitochondrial DNA (mtDNA) variations could discriminate the most frequent type of ovarian cancer, high-grade serous carcinoma (HGSC), from normal tissue.

Microbial Communities in Gynecological Cancers and Their Association with Tumor Somatic Variation.

There are strong correlations between the microbiome and human disease, including cancer. However, very little is known about potential mechanisms associated with malignant transformation in microbiome-associated gynecological cancer, except for HPV-induced cervical cancer. Our hypothesis is that differences in bacterial communities in upper genital tract epithelium may lead to selection of specific genomic variation at the cellular level of these tissues that may predispose to their malignant transformation.

Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile.

Objective: To identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.

Methods: We searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of and expression and sequence variations in , , or (ECPPF) to prognostically stratify MSI-H/NSMP ECs.

FGFR2 mutations promote endometrial cancer progression through dual engagement of EGFR and Notch signalling pathways.

Background: Mutations in the receptor tyrosine kinase gene fibroblast growth factor receptor 2 (FGFR2) occur at a high frequency in endometrial cancer (EC) and have been linked to advanced and recurrent disease. However, little is known about how these mutations drive carcinogenesis.

Methods: Differential transcriptomic analysis and two-step quantitative real-time PCR (qRT-PCR) assays were applied to identify genes differentially expressed in two cohorts of EC patients carrying mutations in the FGFR2 gene as well as in EC cells harbouring mutations in the FGFR2.

Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma.

Background: Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior studies were largely platform-specific and unable to evaluate multiple molecular features.

Methods: We analyzed genome-wide DNA methylation in 1,040 frozen HGSC, including 325 previously reported upon, seeking a multi-platform quantitative methylation signature that we evaluated in relation to clinical features, tumor characteristics, time to recurrence/death, extent of CD8+ tumor-infiltrating lymphocytes (TIL), gene expression molecular subtypes, and gene expression of the ATP-binding cassette transporter TAP1.

Integration of Genomic and Clinical Retrospective Data to Predict Endometrioid Endometrial Cancer Recurrence.

Endometrial cancer (EC) incidence and mortality continues to rise. Molecular profiling of EC promises improvement of risk assessment and treatment selection. However, we still lack robust and accurate models to predict those at risk of failing treatment.

Using Genomic Variation to Distinguish Ovarian High-Grade Serous Carcinoma from Benign Fallopian Tubes.

Unlabelled: The preoperative diagnosis of pelvic masses has been elusive to date. Methods for characterization such as CA-125 have had limited specificity. We hypothesize that genomic variation can be used to create prediction models which accurately distinguish high grade serous ovarian cancer (HGSC) from benign tissue.

ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification: Profiling high-risk subtypes of histomorphologically low-risk and treatment-insensitive endometrioid endometrial cancer.

In endometrial cancer, occult high-risk subtypes (rooted in histomorphologically low-risk disease) with insensitivity to adjuvant therapies impede improvements in therapeutic efficacy. Therefore, we aimed to assess the ability of molecular high-risk (MHR) and low-risk (MLR) ECPPF (E2F1, CCNA2, POLE, PPP2R1A, FBXW7) stratification to profile recurrence in early, low-risk endometrioid endometrial cancer (EEC) and insensitivity to platinum-based chemotherapy or radiotherapy (or both) in high-risk EEC. Using The Cancer Genome Atlas endometrial cancer database, we identified 192 EEC cases with available DNA sequencing and RNA expression data.

Association of Distance to Gynecologic Oncologist and Survival in a Rural Midwestern State.

Objectives: Rural ovarian cancer patients experience worse survival compared to urban patients. We assessed whether distance to gynecologic oncology specialists was associated with survival for patients in a rural state.

Methods: Demographic, tumor, and treatment characteristics were extracted from the Iowa Cancer Registry for patients diagnosed between 1990 and 2018.

Integrated Clinical and Genomic Models to Predict Optimal Cytoreduction in High-Grade Serous Ovarian Cancer.

Advanced high-grade serous (HGSC) ovarian cancer is treated with either primary surgery followed by chemotherapy or neoadjuvant chemotherapy followed by interval surgery. The decision to proceed with surgery primarily or after chemotherapy is based on a surgeon's clinical assessment and prediction of an optimal outcome. Optimal and complete cytoreductive surgery are correlated with improved overall survival.

Investigating the effect of optimal cytoreduction in the context of platinum sensitivity in high-grade serous ovarian cancer.

Introduction: The survival benefits of surgical cytoreduction in ovarian cancer are well-established. However, the surgical outcome has never been assessed while controlling for the efficacy of chemotherapy. This leaves the possibility that cytoreduction may not be beneficial for patients whose cancer does not respond well to adjuvant treatment.

Disparity of ovarian cancer survival between urban and rural settings.

Objective: To determine if there is a difference in overall survival of patients with epithelial ovarian cancer in rural, urban, and metropolitan settings in the United States.

Methods: We performed a retrospective cohort study using 2004-2016 National Cancer Database (NCDB) data including high and low grade, stage I-IV disease. Bivariate analyses used Student's t-test for continuous variables and χ test for dichotomous variables.

The Synthetic Curcumin Analog HO-3867 Rescues Suppression of PLAC1 Expression in Ovarian Cancer Cells.

Elevated expression of placenta-specific protein 1 (PLAC1) is associated with the increased proliferation and invasiveness of a variety of human cancers, including ovarian cancer. Recent studies have shown that the tumor suppressor p53 directly suppresses PLAC1 transcription. However, mutations in p53 lead to the loss of PLAC1 transcriptional suppression.

A nuclear polymorphism at the 8q24 region is associated with improved survival time and chemo-response in high-grade serous ovarian cancer.

The 8q24 chromosomal region is strongly associated with an increased risk of ovarian cancer. One single nucleotide polymorphism that is associated with ovarian cancer in this region is rs6983267, located within the long non-coding RNA colon cancer associated transcript 2 (CCAT2). The aim of the present study was to assess the association between rs6983267 and clinical outcomes in patients with high-grade serous ovarian cancer (HGSOC).

Identifying novel ovarian tumor biomarkers through mining of the transcriptome of circulating immune cells: A proof-of-concept study.

Objective: Treatment of high-grade serous ovarian cancer (HGSOC) will benefit from early detection of cancer. Here, we provide proof-of-concept data supporting the hypothesis that circulating immune cells, because of their early recognition of tumors and the tumor microenvironment, can be considered for biomarker discovery.

Methods: Longitudinal blood samples from C57BL/6 mice bearing syngeneic ovarian tumors and peripheral blood mononuclear cells (PBMC) from healthy postmenopausal women and newly diagnosed for HGSOC patients were subjected to RNASeq.

Identification of Novel Fusion Transcripts in High Grade Serous Ovarian Cancer.

Fusion genes are structural chromosomal rearrangements resulting in the exchange of DNA sequences between genes. This results in the formation of a new combined gene. They have been implicated in carcinogenesis in a number of different cancers, though they have been understudied in high grade serous ovarian cancer.

PP2A and E3 ubiquitin ligase deficiencies: Seminal biological drivers in endometrial cancer.

Objective: PI3K-AKT pathway mutations initiate a kinase cascade that characterizes endometrial cancer (EC). As kinases seldom cause oncogenic transformation without dysregulation of antagonistic phosphatases, pivotal interactions governing this pathway were explored and correlated with clinical outcomes.

Methods: After exclusion of patients with POLE mutations from The Cancer Genome Atlas EC cohort with endometrioid or serous EC, the study population was 209 patients with DNA sequencing, quantitative gene-specific RNA expression, copy number variation (CNV), and surveillance data available.

Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome.

Bacteria, archaea, and viruses are associated with numerous human cancers. To date, microbiome variations in transcription have not been evaluated relative to upper female genital tract cancer risk. Our aim was to assess differences in bacterial, archaea, and viral transcript (BAVT) expression between different gynecological cancers and normal fallopian tubes.