A retrospective study for investigating the relationship between old and new staging systems with prognosis in ovarian cancer using gynecologic cancer registry of Japan Society of Obstetrics and Gynecology (JSOG): disparity between serous carcinoma and clear cell carcinoma

Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its chemoresistance and frequent late diagnosis, and suggesting that a more effective treatment approach is needed. Lysyl oxidase (LOX) is involved in important biological processes such as gene regulation, cell signaling and cell motility, its deregulation contributing to tumor formation and development. Although it is known that LOX is involved in proliferation, migration and invasion in several types of tumors, studies of LOX in ovarian cancers are scarce. To explore the molecular regulation mechanisms in ovarian cancer tumorigenesis, the expression change and the function of LOX was confirmed in ovarian tissues and cells, which suggested that LOX is a tumor suppressor gene. To further understand how LOX expression is regulated in ovarian cancer, microRNAs(miRNAs) were considered because of their role in post-transcriptional regulation of many genes. Recent work has described differential expression of mature miRNAs in human cancers. Bioinformatics prediction which was used to find the appropriate miRNA regulating LOX, revealed that miR-29b regulates LOX protein level via its binding site on the 3'UTR of LOX mRNAin ES-2 cells, a human ovarian clear cell carcinoma cell line. miR-29b knockdown inhibited proliferation and invasion in ES-2 cells. Taken together, these findings suggest that influencing LOX regulation bychanging the level of miR-29b expression could provide a novel potential approachfor treating human ovarian clear cell carcinoma.

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ES-2 Ovarian Cancer Cells Present a Genomic Profile Inconsistent with their Reported History

10.21203/rs.3.rs-28022/v1 ◽

2020 ◽

Author(s):

Eric J. Devor ◽

Jace R. Lapierre ◽

Kimberly K. Leslie ◽

David P. Bender

Keyword(s):

Ovarian Cancer ◽

Cell Carcinoma ◽

Cancer Cells ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Serous Carcinoma ◽

Ovarian Cancer Cells ◽

African American Patient ◽

American Patient ◽

Carcinoma Of The Ovary

Abstract Objective: ES-2 ovarian cancer cells have long been reported to have originated from a primary clear cell carcinoma of the ovary presenting in a 47 year-old African American patient. Two recent publications have offered evidence calling both of these characteristics into question. Our objective was to further study this cell line using quantitative real-time PCR (qPCR) and mitochondrial DNA (mtDNA) sequencing in order to confirm or refute these inconsistencies.Results: qPCR assays on two characteristic loci, hepatocyte nuclear factor 1β (NHF-1β) and glutathione peroxidase 3 (GPX3), suggest that ES-2 are unusual clear cell carcinoma cells that appear more like high grade serous carcinoma than clear cell. Further, mtDNA haplotyping places the ancestral origin of the patient’s lineage in the Middle East or Europe and not Africa. These results are consistent with and support the conclusions of the two recent publications.

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Systematic Identification of Characteristic Genes of Ovarian Clear Cell Carcinoma Compared with High-Grade Serous Carcinoma Based on RNA-Sequencing

International Journal of Molecular Sciences ◽

10.3390/ijms20184330 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4330 ◽

Cited By ~ 5

Author(s):

Saya Nagasawa ◽

Kazuhiro Ikeda ◽

Kuniko Horie-Inoue ◽

Sho Sato ◽

Atsuo Itakura ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Carcinoma ◽

Rna Sequencing ◽

Functional Annotation ◽

Molecular Mechanisms ◽

Clear Cell ◽

Sequence Data ◽

Clear Cell Carcinoma ◽

Serous Carcinoma ◽

High Grade

Objective: Ovarian cancer has the highest mortality among gynecological cancers. High-grade serous carcinoma (HGSC) is the most common histotype of ovarian cancer regardless of ethnicity, whereas clear cell carcinoma (CCC) is more common in East Asians than Caucasians. The elucidation of predominant signaling pathways in these cancers is the first step towards understanding their molecular mechanisms and developing their clinical management. Methods: RNA sequencing was performed for 27 clinical ovarian specimens from Japanese women. Principal component analysis (PCA) was conducted on the sequence data mapped on RefSeq with normalized read counts, and functional annotation analysis was performed on genes with substantial weights in PCA. Knockdown experiments were conducted on the selected genes on the basis of PCA. Results: Functional annotation analysis of PCA-defined genes showed predominant pathways, such as cell growth regulators and blood coagulators in CCC and transcription regulators in HGSC. Knockdown experiments showed that the inhibition of the calcium-dependent protein copine 8 (CPNE8) and the transcription factor basic helix-loop-helix family member e 41 (BHLHE41) repressed the proliferation of CCC- and HGSC-derived cells, respectively. Conclusions: This study identified CPNE8 and BHLHE41 as characteristic genes for CCC and HGSC, respectively. The systemic identification of differentially expressed genes in CCC and HGSC will provide useful information to understand transcriptomic differences in these ovarian cancers and to further develop potential diagnostic and therapeutic options for advanced disease.

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Treatment Strategies for ARID1A-Deficient Ovarian Clear Cell Carcinoma

Cancers ◽

10.3390/cancers13081769 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1769

Author(s):

Kazuaki Takahashi ◽

Masataka Takenaka ◽

Aikou Okamoto ◽

David D. L. Bowtell ◽

Takashi Kohno

Keyword(s):

Ovarian Cancer ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Immune Checkpoint Blockade ◽

Serous Carcinoma ◽

Histological Subtype ◽

Ovarian Clear Cell Carcinoma ◽

Chemotherapeutic Regimen ◽

Platinum Based Chemotherapy

Ovarian clear cell carcinoma (OCCC) is a histological subtype of ovarian cancer that is more frequent in Asian countries (~25% of ovarian cancers) than in US/European countries (less than 10%). OCCC is refractory to conventional platinum-based chemotherapy, which is effective against high-grade serous carcinoma (HGSC), a major histological subtype of ovarian cancer. Notably, deleterious mutations in SWI/SNF chromatin remodeling genes, such as ARID1A, are common in OCCC but rare in HGSC. Because this complex regulates multiple cellular processes, including transcription and DNA repair, molecularly targeted therapies that exploit the consequences of SWI/SNF deficiency may have clinical efficacy against OCCC. Three such strategies have been proposed to date: prioritizing a gemcitabine-based chemotherapeutic regimen, synthetic lethal therapy targeting vulnerabilities conferred by SWI/SNF deficiency, and immune checkpoint blockade therapy that exploits the high mutational burden of ARID1A-deficient tumor. Thus, ARID1A deficiency has potential as a biomarker for precision medicine of ovarian cancer.

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Clear Cell Carcinoma Compared to Serous Carcinoma in Early Ovarian Cancer: Same Prognosis in a Large Randomized Trial

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181991546 ◽

2009 ◽

Vol 19 (1) ◽

pp. 88-93 ◽

Cited By ~ 43

Author(s):

P. J. Timmers ◽

A. H. Zwinderman ◽

I. Teodorovic ◽

I. Vergote ◽

J. B. Trimbos

Keyword(s):

Ovarian Cancer ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Disease Free Survival ◽

Serous Carcinoma ◽

Free Survival ◽

Gynecology And Obstetrics ◽

Significant Difference ◽

Early Ovarian Cancer ◽

Disease Free

Background:An analysis was performed comparing survival of patients with clear cell carcinoma (CCC) to patients with serous adenocarcinoma (SAC) in early ovarian cancer. Furthermore, a literature search was done to clarify the clinical and histopathological features of clear cell tumors of the ovary.Methods:Between November 1990 and March 2000, 448 patients with ovarian cancer International Federation of Gynecology and Obstetrics stages I to IIa were enrolled in the European Organisation for Research and Treatment of Cancer-Adjuvant Chemotherapy in Ovarian Neoplasm Trial, a randomized study comparing adjuvant platinum-based chemotherapy to observation after surgical treatment in patients with early ovarian cancer.Results:Sixty-three patients (14.1%) with CCC were compared with 156 patients (34.8%) with serous tumors. A significant difference was found in the International Federation of Gynecology and Obstetrics stage Ic with capsule rupture, 28 (44.4%) of 63 patients with CCC and 29 (18.6%) of 156 patients with SAC (P < 0.001). Recurrences occurred in 25% of the patients, and this was similar in the CCC and SAC groups. No significant difference was found in overall survival between patients with CCC and patients with SAC in both treatment arms together. In the observation arm, the 5-year disease-free survival was 71% in the CCC group versus 61% in the SAC group, whereas in the chemotherapy arm, the 5-year disease-free survival was higher in the SAC group compared with the CCC group (78% vs 60%). Both differences were not statistically significant.Conclusions:The present study showed no worse prognosis in patients with CCC as compared with patients with serous carcinoma in early ovarian cancer.

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An evaluation of progression-free survival (PFS) and overall survival (OS) of ovarian cancer patients with clear cell carcinoma vs serous carcinoma treated with platinum therapy: A Gynecologic Oncology Group (GOG) experience

Gynecologic Oncology ◽

10.1016/j.ygyno.2014.03.085 ◽

2014 ◽

Vol 133 ◽

pp. 26-27

Author(s):

K.E. Oliver ◽

W.E. Brady ◽

M.J. Birrer ◽

D.M. Gershenson ◽

G. Fleming ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Gynecologic Oncology ◽

Progression Free Survival ◽

Serous Carcinoma ◽

Gynecologic Oncology Group ◽

Oncology Group ◽

Free Survival

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Systematic Identification of Characteristic Genes of Ovarian Clear Cell Carcinoma Compared with High-Grade Serous Carcinoma Based on RNA-Sequencing

10.31234/osf.io/zn3bs ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Ovarian Cancer ◽

Cell Carcinoma ◽

Rna Sequencing ◽

Molecular Mechanisms ◽

Clear Cell ◽

Sequence Data ◽

Clear Cell Carcinoma ◽

Serous Carcinoma ◽

Calcium Dependent ◽

Helix Loop Helix

Objective: Ovarian cancer has the highest mortality among gynecological cancers.High-grade serous carcinoma (HGSC) is the most common histotype of ovarian cancer regardlessof ethnicity, whereas clear cell carcinoma (CCC) is more common in East Asians than Caucasians.The elucidation of predominant signaling pathways in these cancers is the first step towardsunderstanding their molecular mechanisms and developing their clinical management. Methods:RNA sequencing was performed for 27 clinical ovarian specimens from Japanese women. Principalcomponent analysis (PCA) was conducted on the sequence data mapped on RefSeq with normalizedread counts, and functional annotation analysis was performed on genes with substantial weights inPCA. Knockdown experiments were conducted on the selected genes on the basis of PCA. Results:Functional annotation analysis of PCA-defined genes showed predominant pathways, such as cellgrowth regulators and blood coagulators in CCC and transcription regulators in HGSC. Knockdownexperiments showed that the inhibition of the calcium-dependent protein copine 8 (CPNE8) and thetranscription factor basic helix-loop-helix family member e 41 (BHLHE41) repressed the proliferationof CCC- and HGSC-derived cells, respectively. Conclusions: This study identified CPNE8 andBHLHE41 as characteristic genes for CCC and HGSC, respectively. The systemic identification ofdi?erentially expressed genes in CCC and HGSC will provide useful information to understandtranscriptomic di?erences in these ovarian cancers and to further develop potential diagnostic andtherapeutic options for advanced disease.Keywords: ovarian cancer; gene expression; RNA sequencing; clear cell carcinoma; high-gradeserous carcinoma

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