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

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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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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Bilateral synchronous high-grade serous carcinoma and clear cell carcinoma in right and left ovaries with immunohistochemical confirmation: An exceptional finding

Indian Journal of Pathology and Microbiology ◽

10.4103/0377-4929.142706 ◽

2014 ◽

Vol 57 (4) ◽

pp. 623 ◽

Cited By ~ 1

Author(s):

Agarwal Preeti ◽

KumarArun Arunachalam ◽

Yashodhara Pradeep ◽

GoelMadhu Mati

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Serous Carcinoma ◽

High Grade

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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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Establishment of Patient-Derived Tumor Xenograft Models of High-Risk Endometrial Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001365 ◽

2018 ◽

Vol 28 (9) ◽

pp. 1812-1820 ◽

Cited By ~ 1

Author(s):

Menghan Zhu ◽

Nan Jia ◽

Yanyan Nie ◽

Jun Chen ◽

Yahui Jiang ◽

...

Keyword(s):

High Risk ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Tumor Xenograft ◽

Serous Carcinoma ◽

High Grade ◽

Primary Tumors ◽

P53 Expression ◽

Subrenal Capsule

ObjectiveHigh-risk endometrial cancers (ECs), including high-grade EC, serous carcinoma (SC), clear cell carcinoma, and carcinosarcoma, account for 50% of deaths due to ECs. Therapies for these cancers are limited, and patient-derived tumor xenograft (PDTX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies. Here, we used and compared 2 methods to establish PDTX models.MethodsFresh tumor tissues collected from 18 primary high-risk EC patients (10 high-grade ECs, 6 SCs, 1 clear cell carcinoma, and 1 carcinosarcoma) were engrafted subcutaneously and in the subrenal capsule in NOD/SCID for establishment and Balb/c-nu/nu mice for expansion. Histology and cytokeratin, estrogen receptor, progesterone receptor, and P53 expression were evaluated to assess the similarity of primary tumors and different generations of PDTX tumors. Whole-exome sequencing (WES) and RNA sequencing were used in 2 high-grade EC models to verify whether the genetic mutation profiles and gene expression were similar between primary and PDTX tumors.ResultsThe total tumor engraftment rate was 77.8% (14/18) regardless of the engraft method. The tumor engraftment rate was increased in subrenal capsule models compared with subcutaneous models (62.5% vs 50%, P = 0.464). The time to tumor formation varied significantly from 2 to 11 weeks. After subrenal capsular grafting, grafted tumors could be successfully transplanted to subcutaneous sites. We observed good similarity between primary tumors and corresponding different passages of xenografts.ConclusionsThe combination of 2 engrafting methods increases the tumor engraftment rate. The high tumor engraftment rate ensures the establishment of a high-risk EC biobank, which is a powerful resource for performing preclinical drug-sensitivity tests and identifying biomarkers for response or resistance.

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Two cases of high grade tubo-ovarian serous carcinoma with extensive clear cell carcinoma-like morphology, possibly accentuated in the neoadjuvant setting

Human Pathology Case Reports ◽

10.1016/j.ehpc.2017.10.005 ◽

2018 ◽

Vol 11 ◽

pp. 68-72

Author(s):

Madhuchhanda Roy ◽

Paul Weisman

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Serous Carcinoma ◽

High Grade ◽

Ovarian Serous Carcinoma

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Magnetic resonance imaging for distinguishing ovarian clear cell carcinoma from high-grade serous carcinoma

Journal of Ovarian Research ◽

10.1186/s13048-016-0251-x ◽

2016 ◽

Vol 9 (1) ◽

Cited By ~ 8

Author(s):

Feng-Hua Ma ◽

Jin-Wei Qiang ◽

Guo-Fu Zhang ◽

Hai-Ming Li ◽

Song-Qi Cai ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Serous Carcinoma ◽

High Grade ◽

Resonance Imaging ◽

Ovarian Clear Cell Carcinoma

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The Analysis of Cell Cycle–related Proteins in Ovarian Clear Cell Carcinoma Versus High-grade Serous Carcinoma

International Journal of Gynecological Pathology ◽

10.1097/pgp.0000000000000461 ◽

2018 ◽

Vol 37 (6) ◽

pp. 516-524 ◽

Cited By ~ 2

Author(s):

Yukiko Hazama ◽

Takuya Moriya ◽

Mika Sugihara ◽

Rikiya Sano ◽

Mitsuru Shiota ◽

...

Keyword(s):

Cell Cycle ◽

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Serous Carcinoma ◽

High Grade ◽

Ovarian Clear Cell Carcinoma ◽

Related Proteins

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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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