Ovarian cancer (OC) is a frequently lethal gynecologic malignancy, characterized by a poor prognosis and high recurrence rate. The immune microenvironment has been implicated in the progression of OC. We characterized the immune landscape in primary and malignant OC ascites using single-cell and bulk transcriptome raw OC data acquired from the Gene Expression Omnibus and The Cancer Genome Atlas databases. We then used the CIBERSORT deconvolution algorithm, weighted gene co-expression network analysis, univariate and multivariate Cox analyses, and the LASSO algorithm to develop a tumor-associated macrophage-related gene (TAMRG) prognostic signature, which enabled us to stratify and predict overall survival (OS) of OC patients. In addition, inter- and intra-patient heterogeneity of infiltrating immune cells was characterized at single-cell resolution. Tumor-infiltrating macrophages with an M2 phenotype exhibited immunosuppressive activity. M1 macrophages positively correlated with OS, whereas activated mast cells, neutrophils, M2 macrophages, and activated memory CD4 T cells were all negatively correlated with OS. A total of 219 TAMRGs were identified, and a novel 6-gene signature (, , , , , and ) with independent prognostic value was established. These results show that a TAMRG-based signature may be a promising prognostic and therapeutic target in OC.
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http://dx.doi.org/10.18632/aging.203613 | DOI Listing |
Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFJ Ovarian Res
January 2025
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, #128 Shenyang Road, Shanghai, 200090, People's Republic of China.
Background: Ovarian cancers (OC) and cervical cancers (CC) have poor survival rates. Tumor-infiltrating lymphocytes (TILs) play a pivotal role in prognosis, but shared immune mechanisms remain elusive.
Methods: We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore immune regulation in OC and CC, focusing on the PI3K/AKT pathway and FLT3 as key modulators.
Oncogene
January 2025
Department of Gastroenterology, Endocrinology and Metabolism, Center for Tumor and Immune Biology, Philipps University Marburg, Marburg, Germany.
The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated.
View Article and Find Full Text PDFSci Rep
January 2025
Chair of Obstetrics Development, Faculty of Health Sciences, Medical University of Lublin, Lublin, Poland.
The aim of the study is to analyze the relationship between personality traits of women with hereditary predisposition to breast/ovarian cancer and their obstetric history and cancer-preventive behaviors. A total of 357 women, participants of 'The National Program for Families With Genetic/Familial High Risk for Cancer', were included in the study. The Neo Five-Factor Inventory (NEO-FFI) and a standardized original questionnaire designed for the purpose of the study were used.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
Eötvös Loránd University, Department of Physics of Complex Systems, Budapest, Hungary.
Patients with High-Grade Serous Ovarian Cancer (HGSOC) exhibit varied responses to treatment, with 20-30% showing de novo resistance to platinum-based chemotherapy. While hematoxylin-eosin (H&E)-stained pathological slides are used for routine diagnosis of cancer type, they may also contain diagnostically useful information about treatment response. Our study demonstrates that combining H&E-stained whole slide images (WSIs) with proteomic signatures using a multimodal deep learning framework significantly improves the prediction of platinum response in both discovery and validation cohorts.
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