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Open AccessArticle

Transcriptome Profiling Reveals Matrisome Alteration as a Key Feature of Ovarian Cancer Progression

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Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA
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Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Medical Sciences Program, Indiana University School of Medicine—Bloomington, Bloomington, IN 47405, USA
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Center for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47405, USA
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Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
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Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(10), 1513; https://doi.org/10.3390/cancers11101513
Received: 1 August 2019 / Revised: 30 August 2019 / Accepted: 30 September 2019 / Published: 9 October 2019
(This article belongs to the Special Issue Ovarian Cancer Metastasis)
Background: Ovarian cancer is the most lethal gynecologic malignancy. There is a lack of comprehensive investigation of disease initiation and progression, including gene expression changes during early metastatic colonization. Methods: RNA-sequencing (RNA-seq) was done with matched primary tumors and fallopian tubes (n = 8 pairs) as well as matched metastatic and primary tumors (n = 11 pairs) from ovarian cancer patients. Since these are end point analyses, it was combined with RNA-seq using high-grade serous ovarian cancer cells seeded on an organotypic three-dimensional (3D) culture model of the omentum, mimicking early metastasis. This comprehensive approach revealed key changes in gene expression occurring in ovarian cancer initiation and metastasis, including early metastatic colonization. Results: 2987 genes were significantly deregulated in primary tumors compared to fallopian tubes, 845 genes were differentially expressed in metastasis compared to primary tumors and 304 genes were common to both. An assessment of patient metastasis and 3D omental culture model of early metastatic colonization revealed 144 common genes that were altered during early colonization and remain deregulated even in the fully developed metastasis. Deregulation of the matrisome was a key process in early and late metastasis. Conclusion: These findings will help in understanding the key pathways involved in ovarian cancer progression and eventually targeting those pathways for therapeutic interventions. View Full-Text
Keywords: ovarian cancer; fallopian tube; primary tumor; metastasis; gene expression; sequencing; tumor microenvironment; matrisome ovarian cancer; fallopian tube; primary tumor; metastasis; gene expression; sequencing; tumor microenvironment; matrisome
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Mitra, S.; Tiwari, K.; Podicheti, R.; Pandhiri, T.; Rusch, D.B.; Bonetto, A.; Zhang, C.; Mitra, A.K. Transcriptome Profiling Reveals Matrisome Alteration as a Key Feature of Ovarian Cancer Progression. Cancers 2019, 11, 1513.

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