DIFFERENTIALLY EXPRESSED MIRNAS AND THEIR SURVIVAL PREDICTION IN THE HIGH GRADE SEROUS AND CLEAR CELL OVARIAN CARCINOMA: IGCS-0043 06. Ovarian Cancer

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

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Comparison of surgical and oncologic outcomes in patients with clear cell ovarian carcinoma associated with and without endometriosis

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-021-06096-6 ◽

2021 ◽

Author(s):

Ruja Charatsingha ◽

Suchanan Hanamornroongruang ◽

Mongkol Benjapibal ◽

Suwanit Therasakvichya ◽

Atthapon Jaishuen ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Clear Cell ◽

Oncologic Outcomes ◽

Clear Cell Ovarian Carcinoma

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The role of FOXC1 in clear cell ovarian carcinoma: Potential prognostic biomarker for aggressive disease?

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.07.083 ◽

2015 ◽

Vol 139 (1) ◽

pp. 204

Author(s):

T.J. Vogel ◽

J. Cohen ◽

B. Han ◽

A.E. Walts ◽

X. Zhang ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Clear Cell ◽

Prognostic Biomarker ◽

Aggressive Disease ◽

Clear Cell Ovarian Carcinoma

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GATA3 and stemness of high-grade serous ovarian carcinoma: novel hope for the deadliest type of ovarian cancer

Human Cell ◽

10.1007/s13577-020-00368-0 ◽

2020 ◽

Vol 33 (3) ◽

pp. 904-906 ◽

Cited By ~ 1

Author(s):

Amr Ahmed El-Arabey ◽

Mohnad Abdalla ◽

Adel Rashad Abd-Allah

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

High Grade ◽

Serous Ovarian Carcinoma

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Mechanisms of Chromosomal Instability in High-grade Serous Ovarian Carcinoma

10.1101/727537 ◽

2019 ◽

Cited By ~ 1

Author(s):

N. Tamura ◽

N. Shaikh ◽

D. Muliaditan ◽

J. McGuinness ◽

D. Moralli ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Single Molecule ◽

Chromosomal Instability ◽

Poor Prognosis ◽

Spindle Assembly Checkpoint ◽

Western World ◽

Cancer Type ◽

High Grade ◽

Serous Ovarian Carcinoma

AbstractChromosomal instability (CIN), the continual gain and loss of chromosomes or parts of chromosomes, occurs in the majority of cancers and confers poor prognosis. Mechanisms driving CIN remain unknown in most cancer types due to a scarcity of functional studies. High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, is the major cause of death due to gynaecological malignancy in the Western world with chemotherapy resistance developing in almost all patients. HGSC exhibits high rates of chromosome aberrations and knowledge of causative mechanisms is likely to represent an important step towards combating the poor prognosis of this disease. However, very little is known about the nature of chromosomal instability exhibited by this cancer type in particular due to a historical lack of appropriate cell line models. Here we perform the first in-depth functional characterisation of mechanisms driving CIN in HGSC by analysing eight cell lines that accurately recapitulate HGSC genetics as defined by recent studies. We show, using a range of established functional CIN assays combined with live cell imaging and single molecule DNA fibre analysis, that multiple mechanisms co-exist to drive CIN in HGSC. These include supernumerary centrosomes, elevated microtubule dynamics and DNA replication stress. By contrast, the spindle assembly checkpoint was intact. These findings are relevant for developing therapeutic approaches to manipulating CIN in ovarian cancer, and suggests that such approaches may need to be multimodal to combat multiple co-existing CIN drivers.

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The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

Communications Biology ◽

10.1038/s42003-021-02992-4 ◽

2022 ◽

Vol 5 (1) ◽

Author(s):

Hidenori Machino ◽

Syuzo Kaneko ◽

Masaaki Komatsu ◽

Noriko Ikawa ◽

Ken Asada ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Cell Cycle Progression ◽

Target Genes ◽

Metabolic Stress ◽

Ovarian Cancer Cells ◽

Hippo Signaling ◽

High Grade ◽

Gynecological Malignancy ◽

Serous Ovarian Carcinoma

AbstractHigh-grade serous ovarian carcinoma (HGSOC) is the most aggressive gynecological malignancy, resulting in approximately 70% of ovarian cancer deaths. However, it is still unclear how genetic dysregulations and biological processes generate the malignant subtype of HGSOC. Here we show that expression levels of microtubule affinity-regulating kinase 3 (MARK3) are downregulated in HGSOC, and that its downregulation significantly correlates with poor prognosis in HGSOC patients. MARK3 overexpression suppresses cell proliferation and angiogenesis of ovarian cancer cells. The LKB1-MARK3 axis is activated by metabolic stress, which leads to the phosphorylation of CDC25B and CDC25C, followed by induction of G2/M phase arrest. RNA-seq and ATAC-seq analyses indicate that MARK3 attenuates cell cycle progression and angiogenesis partly through downregulation of AP-1 and Hippo signaling target genes. The synthetic lethal therapy using metabolic stress inducers may be a promising therapeutic choice to treat the LKB1-MARK3 axis-dysregulated HGSOCs.

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