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Open AccessArticle

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

1
Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241, Japan
2
Department of Obstetrics and Gynecology, Juntendo University, Tokyo 113-8421, Japan
3
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan
4
Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute of Gerontology Itabashi-ku, Tokyo 173-0015, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4330; https://doi.org/10.3390/ijms20184330
Received: 30 July 2019 / Revised: 25 August 2019 / Accepted: 2 September 2019 / Published: 4 September 2019
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. View Full-Text
Keywords: ovarian cancer; gene expression; RNA sequencing; clear cell carcinoma; high-grade serous carcinoma ovarian cancer; gene expression; RNA sequencing; clear cell carcinoma; high-grade serous carcinoma
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MDPI and ACS Style

Nagasawa, S.; Ikeda, K.; Horie-Inoue, K.; Sato, S.; Itakura, A.; Takeda, S.; Hasegawa, K.; Inoue, S. Systematic Identification of Characteristic Genes of Ovarian Clear Cell Carcinoma Compared with High-Grade Serous Carcinoma Based on RNA-Sequencing. Int. J. Mol. Sci. 2019, 20, 4330. https://doi.org/10.3390/ijms20184330

AMA Style

Nagasawa S, Ikeda K, Horie-Inoue K, Sato S, Itakura A, Takeda S, Hasegawa K, Inoue S. 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. 2019; 20(18):4330. https://doi.org/10.3390/ijms20184330

Chicago/Turabian Style

Nagasawa, Saya; Ikeda, Kazuhiro; Horie-Inoue, Kuniko; Sato, Sho; Itakura, Atsuo; Takeda, Satoru; Hasegawa, Kosei; Inoue, Satoshi. 2019. "Systematic Identification of Characteristic Genes of Ovarian Clear Cell Carcinoma Compared with High-Grade Serous Carcinoma Based on RNA-Sequencing" Int. J. Mol. Sci. 20, no. 18: 4330. https://doi.org/10.3390/ijms20184330

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