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Molecular Research on Gynecological Cancers: Ovarian Cancer, Endometrial Cancer, and Gestational Trophoblastic Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 1100

Special Issue Editors


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Guest Editor
Institute of Pathology, Medical Area Department, University of Udine-Azienda Sanitaria Universitaria Friuli Centrale-ASUFC, P.le S. Maria della Misericordia, 15-33100 Udine, Italy
Interests: histopathology; gynecological cancers; breast cancer; molecular biology; tissue regeneration; stem cell biology

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Guest Editor
Pathology Resident at the Institute of Pathology, Medical Area Department, University of Udine-Azienda Sanitaria Universitaria Friuli Centrale-ASUFC, P.le S. Maria della Misericordia, 15-33100 Udine, Italy
Interests: pathology; cancer research; gynecological cancers; neuroendocrine tumors; immuno-oncology; tumor microenvironment; complement system

E-Mail Website
Guest Editor
Institute of Pathology, Medical Area Department, University of Udine, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), P.le S. Maria della Misericordia, 15-33100 Udine, Italy
Interests: pathology; cancer research; gynecological cancers; gestational trophoblastic disease; breast cancer; feto-placental pathology; perinatal pathology

Special Issue Information

Dear Colleagues,

Ovarian and endometrial cancers are the most prevalent and deadliest gynecological malignancies worldwide, constituting a great challenge for all who participate in patient diagnosis and treatment. Over recent years, conventional therapeutic options, such as surgery, chemotherapy, and radiotherapy, have been overcome by emerging approaches, allowing development towards a more comprehensive overview of cancer etiology and evolution. Advances in the treatment of gynecological neoplasms have fueled passionate debate in conversations including not only surgeons, oncologists, and radiotherapists, but also other professional figures, such as pathologists, molecular biologists, and geneticists. Thus, multi-disciplinarity has become the ace in the hole in terms of establishing increasingly personalized treatments. Patients life expectancy is rising, opening new questions for the management of cancer survivors.

Although relatively rare, gestational trophoblastic disease represents another serious public health issue for women of reproductive age. In particular, tumors arising from extraembryonic tissues are extraordinary with respect to their fetal origin (semi-allograft) and the maternal tissue matrix (endomyometrium) that supports their growth. Gestational trophoblastic disease consists of well-defined diagnostic entities of a proliferative disorder of the placenta, of which hydatidiform moles are common lesions. Even with available ancillary studies, including ploidy and immunohistochemistry analyses, histological diagnosis of molar pregnancies can be challenging in a significant percentage of the cases. PCR-based short-tandem repeat DNA genotyping has emerged as a powerful ancillary tool for the precise diagnosis and subclassification of gestational trophoblastic diseases, particularly hydatidiform moles. As lesions of gestational origin, the inherited paternal genome, with or without copy number alterations, is the fundamental molecular basis for the diagnostic applications of DNA genotyping. Genotyping is now considered the gold standard in confirming and subtyping sporadic hydatidiform moles. Beyond hydatidiform moles, DNA genotyping also has fundamental applications in the diagnosis or prognostic assessment of gestational trophoblastic tumors, particularly gestational choriocarcinoma.

Malignant transformation in gestational trophoblastic tumors is likely a multistep process involving multiple genetic alterations, as with other human cancers, and may involve the activation of oncogenes and inactivation of tumor suppressor genes. In addition, expression of telomerase activity, altered expression of cell–cell adhesion molecules, and abnormal expression of matrix metalloproteinases have also been reported in gestational trophoblastic disease. These represent the disruption of the delicate balance and regulation of cellular processes, including proliferation, differentiation, apoptosis, and invasion.

In this Special Issue, we invite experts in the field to review the current diagnostic, therapeutic, and experimental models of gynecological cancers. We invite the submission of research articles that help to clarify the mechanisms underlying tumor heterogeneity/microenvironment, the diverse molecular signatures of gynecological cancers (epigenome, immune landscape, dysregulation of phylogenetically conserved signaling pathways), and the relative contribution of cancer stem cells. Additionally, we welcome studies conducted to unveil the molecular alterations exhibited by tumor cells, the proposal of novel targets for cancer therapy, and the mechanisms of action of drugs and drug candidates (including off-target effects and drug repurposing). In addition, we aim to promote the diffusion of review articles that highlight new findings in the above areas and underline similarities or cross-comparisons between gynecological cancers and other human malignancies.

Dr. Laura Mariuzzi
Dr. Alessandro Mangogna
Dr. Maria Orsaria
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ovarian cancer
  • endometrial cancer
  • gestational trophoblastic disease
  • prognostic factors
  • oncogenes
  • molecular genetics and genomics
  • DNA genotyping
  • cancer stem cells
  • epigenomics
  • signaling pathways
  • extracellular vesicles
  • tumour heterogeneity
  • tumour microenvironment
  • immune checkpoint inhibitors
  • new targets
  • molecular target

Published Papers (1 paper)

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Research

27 pages, 12242 KiB  
Article
PRKDC-Mediated NHEJ May Play a Crucial Role in Aneuploidy of Chromosome 8-Driven Progression of Ovarian Cancer
by Wenqing Luan, Hongyan Cheng, Haoling Xie, Huiping Liu, Yicheng Wang, Shang Wang, Xue Ye, Honglan Zhu, Fuchou Tang, Yi Li and Xiaohong Chang
Int. J. Mol. Sci. 2024, 25(9), 4825; https://doi.org/10.3390/ijms25094825 - 28 Apr 2024
Viewed by 298
Abstract
High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features [...] Read more.
High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and hub–gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that PRKDC gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of PRKDC, has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of PRKDC in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. PRKDC and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC. Full article
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