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Molecular Research on Obstetrics and Gynecology
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Molecular Research on Obstetrics and Gynecology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 18357

Special Issue Editors

Dr. Pasquale De Franciscis

E-Mail Website
Guest Editor
Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: endometriosis; endometrial pathology; minimally invasive surgery
Special Issues, Collections and Topics in MDPI journals
Dr. Gaetano Riemma

E-Mail Website
Guest Editor
Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli”, Naples, Italy
Interests: endometriosis; endometrial pathology; minimally invasive surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Our knowledge relating to the theoretical and clinical aspects in the field of medicine has increased exponentially in recent years.

Benign (including endometrial pathology, uterine fibroids, endometriosis, and ovarian disorders) and malignant (including endometrial, cervical, and ovarian cancer) gynecological pathologies represent, respectively, the most common and most harmful diseases affecting women’s health.

The molecular approach to gynecology is, therefore, an interesting option to understand cellular mechanisms and hormonal pathways in order to diagnose early and better treat these pathologies.

This Special Issue is focused on publishing outstanding research in molecular, precision-based approaches that may open up new fields and bring forth new points of view.

Regarding cervical cancer, diagnostic techniques for human papillomavirus detection and genotyping represents an intriguing option in order to detect the high-risk strains and amplify fragments of DNA from a targeted gene sequence. In endometrial cancer, a molecular approach involving the TCGA (The Cancer Genome Atlas) group, microsatellite instability molecular testing, as well as copy-number-low/p53-wild-type (p53wt), POLE-mutated/ultramutated (POLEmt) are crucial for understanding the prognostic value of the neoplasm and choosing the appropriate surgical and clinical management.

New evidence is showing a promising role of micro-RNAs as potential biomarkers for endometriosis and for the pathophysiology of uterine fibroids, unravelling new pathogenetic and therapeutic pathways. For this reason, a molecular, precision-based approach is undoubtfully important also in benign gynecological diseases.

To date, several issues have arisen around the technical elements of molecular biomarkers, and therapies and have not yet fulfilled their expectations. Concerning benign and malignant gynecology, new molecular discoveries are influenced by technical issues such as test sensitivity and genetic heterogeneity. As molecular medicine becomes a more integral part of routine medical practice, it is fundamental that healthcare providers be aware of advances in the understanding of how several benign and malignant gynecological diseases can benefit from a precision-based approach, in order to improve the efficacy and impact of the standard of care, affecting women’s health and wellbeing.

This collection will not be limited to clinical work about diagnosis, or clinical and surgical managements, but it will specifically involve basic science (immunobiology, cellular and molecular biology, genetics, and epigenetics), to deepen the actual knowledge and discover new fields for the future diagnosis and treatment of uterine and cervical pathologies, endometriosis, ovarian diseases, as well as the precision-based approach to infertility and gynecological malignancies.

Dr. Pasquale De Franciscis
Dr. Gaetano Riemma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • Precision medicine
  • Cancer immunology
  • Biomarkers
  • Infertility
  • Minimally invasive gynecology
  • Molecular testing
  • Endometrial cancer
  • Ovarian cancer
  • Cervical cancer
  • Ovarian neoplasms
  • Endometriosis
  • Uterine fibroids
  • Epigenetics

Published Papers (5 papers)

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Research

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13 pages, 9719 KiB  
Article
Mesothelin Expression Is Not Associated with the Presence of Cancer Stem Cell Markers SOX2 and ALDH1 in Ovarian Cancer
by Mariana Nunes, Francisca Pacheco, Ricardo Coelho, Dina Leitão, Sara Ricardo and Leonor David
Int. J. Mol. Sci. 2022, 23(3), 1016; https://doi.org/10.3390/ijms23031016 - 18 Jan 2022
Cited by 1 | Viewed by 2243
Abstract
Mesothelin (MSLN) overexpression (OE) is a frequent finding in ovarian carcinomas and increases cell survival and tumor aggressiveness. Since cancer stem cells (CSCs) contribute to pathogenesis, chemoresistance and malignant behavior in ovarian cancer (OC), we hypothesized that MSLN expression could be creating a [...] Read more.
Mesothelin (MSLN) overexpression (OE) is a frequent finding in ovarian carcinomas and increases cell survival and tumor aggressiveness. Since cancer stem cells (CSCs) contribute to pathogenesis, chemoresistance and malignant behavior in ovarian cancer (OC), we hypothesized that MSLN expression could be creating a favorable environment that nurtures CSCs. In this study, we analyzed the expression of MSLN and CSC markers SOX2 and ALDH1 by immunohistochemistry (IHC) in different model systems: primary high-grade serous carcinomas (HGSCs) and OC cell lines, including cell lines that were genetically engineered for MSLN expression by either CRISPR-Cas9-mediated knockout (Δ) or lentivirus-mediated OE. Cell lines, wild type and genetically engineered, were evaluated in 2D and 3D culture conditions and xenografted in nude mice. We observed that MSLN was widely expressed in HGSC, and restricted expression was observed in OC cell lines. In contrast, SOX2 and ALDH1 expression was limited in all tissue and cell models. Most importantly, the expression of CSC markers was independent of MSLN expression, and manipulation of MSLN expression did not affect CSC markers. In conclusion, MSLN expression is not involved in driving the CSC phenotype. Full article
(This article belongs to the Special Issue Molecular Research on Obstetrics and Gynecology)
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17 pages, 3007 KiB  
Article
A Keratin 7 and E-Cadherin Signature Is Highly Predictive of Tubo-Ovarian High-Grade Serous Carcinoma Prognosis
by Laudine Communal, Noemi Roy, Maxime Cahuzac, Kurosh Rahimi, Martin Köbel, Diane M. Provencher and Anne-Marie Mes-Masson
Int. J. Mol. Sci. 2021, 22(10), 5325; https://doi.org/10.3390/ijms22105325 - 18 May 2021
Cited by 15 | Viewed by 3141
Abstract
During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard epithelial markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, [...] Read more.
During tubo-ovarian high-grade serous carcinoma (HGSC) progression, tumoral cells undergo phenotypic changes in their epithelial marker profiles, which are essential for dissemination processes. Here, we set out to determine whether standard epithelial markers can predict HGSC patient prognosis. Levels of E-CADH, KRT7, KRT18, KRT19 were quantified in 18 HGSC cell lines by Western blot and in a Discovery cohort tissue microarray (TMA) (n = 101 patients) using immunofluorescence. E-CADH and KRT7 levels were subsequently analyzed in the TMA of the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n = 1158 patients) and in public datasets. Epithelial marker expression was highly variable in HGSC cell lines and tissues. In the Discovery cohort, high levels of KRT7 and KRT19 were associated with an unfavorable prognosis, whereas high E-CADH expression indicated a better outcome. Expression of KRT7 and E-CADH gave a robust combination to predict overall survival (OS, p = 0.004) and progression free survival (PFS, p = 5.5 × 10−4) by Kaplan–Meier analysis. In the COEUR cohort, the E-CADH-KRT7 signature was a strong independent prognostic biomarker (OS, HR = 1.6, p = 2.9 × 10−4; PFS, HR = 1.3, p = 0.008) and predicted a poor patient response to chemotherapy (p = 1.3 × 10−4). Our results identify a combination of two epithelial markers as highly significant indicators of HGSC patient prognosis and treatment response. Full article
(This article belongs to the Special Issue Molecular Research on Obstetrics and Gynecology)
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10 pages, 3748 KiB  
Article
Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts
by Paweł Uruski, Justyna Mikuła-Pietrasik, Martyna Pakuła, Sylwia Budkiewicz, Marcin Drzewiecki, Andrey N. Gaiday, Małgorzata Wierzowiecka, Eryk Naumowicz, Rafał Moszyński, Andrzej Tykarski and Krzysztof Książek
Int. J. Mol. Sci. 2021, 22(8), 4222; https://doi.org/10.3390/ijms22084222 - 19 Apr 2021
Cited by 13 | Viewed by 2338
Abstract
Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on [...] Read more.
Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-β1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-β1, GRO-1, and IGF-1. Moreover, MAs upregulated α5β1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells. Full article
(This article belongs to the Special Issue Molecular Research on Obstetrics and Gynecology)
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16 pages, 1769 KiB  
Article
Genomic and Epigenomic Profile of Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMPs) Revealed Similarities and Differences with Leiomyomas and Leiomyosarcomas
by Donatella Conconi, Serena Redaelli, Andrea Alberto Lissoni, Chiara Cilibrasi, Patrizia Perego, Eugenio Gautiero, Elena Sala, Mariachiara Paderno, Leda Dalprà, Fabio Landoni, Marialuisa Lavitrano, Gaia Roversi and Angela Bentivegna
Int. J. Mol. Sci. 2021, 22(4), 1580; https://doi.org/10.3390/ijms22041580 - 4 Feb 2021
Cited by 10 | Viewed by 2255
Abstract
Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) represent a heterogeneous group of tumors that cannot be histologically diagnosed as unequivocally benign or malignant. For this reason, many authors are working to obtain a better definition of diagnostic and prognostic criteria. In [...] Read more.
Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) represent a heterogeneous group of tumors that cannot be histologically diagnosed as unequivocally benign or malignant. For this reason, many authors are working to obtain a better definition of diagnostic and prognostic criteria. In this work, we analyzed the genomic and epigenomic profile of uterine smooth muscle tumors (USMTs) in order to find similarities and differences between STUMPs, leiomyosarcomas (LMSs) and leiomyomas (LMs), and possibly identify prognostic factors in this group of tumors. Array-CGH data on 23 USMTs demonstrated the presence of a more similar genomic profile between STUMPs and LMSs. Some genes, such as PRKDC and PUM2, with a potential prognostic value, were never previously associated with STUMP. The methylation data appears to be very promising, especially with regards to the divergent profile found in the sample that relapsed, characterized by an overall CGI hypomethylation. Finally, the Gene Ontology analysis highlighted some cancer genes that could play a pivotal role in the unexpected aggressive behavior that can be found in some of these tumors. These genes could prove to be prognostic markers in the future. Full article
(This article belongs to the Special Issue Molecular Research on Obstetrics and Gynecology)
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Review

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25 pages, 611 KiB  
Review
The Role of Genital Tract Microbiome in Fertility: A Systematic Review
by Salvatore Giovanni Vitale, Federico Ferrari, Michał Ciebiera, Magdalena Zgliczyńska, Agnese Maria Chiara Rapisarda, Giada Maria Vecchio, Alessandra Pino, Giuseppe Angelico, Anna Knafel, Gaetano Riemma, Pasquale De Franciscis and Stefano Cianci
Int. J. Mol. Sci. 2022, 23(1), 180; https://doi.org/10.3390/ijms23010180 - 24 Dec 2021
Cited by 35 | Viewed by 6641
Abstract
The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies [...] Read more.
The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted. Full article
(This article belongs to the Special Issue Molecular Research on Obstetrics and Gynecology)
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