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Nesprin1 Deficiency Is Associated with Poor Prognosis of Renal Cell Carcinoma and Resistance to Sunitinib Treatment

https://hiroshima.repo.nii.ac.jp/records/2007901
https://hiroshima.repo.nii.ac.jp/records/2007901
a5fd18fb-a091-4d38-984c-eeab0167f109
名前 / ファイル ライセンス アクション
Oncology_102_868.pdf Oncology_102_868.pdf (323.2 KB)
Item type デフォルトアイテムタイプ_(フル)(1)
公開日 2024-12-17
タイトル
タイトル Nesprin1 Deficiency Is Associated with Poor Prognosis of Renal Cell Carcinoma and Resistance to Sunitinib Treatment
言語 en
作成者 Fukushima, Takafumi

× Fukushima, Takafumi

en Fukushima, Takafumi

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Kobatake, Kohei

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en Kobatake, Kohei

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Miura, Kento

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en Miura, Kento

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Takemoto, Kenshiro

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en Takemoto, Kenshiro

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Yamanaka, Ryoken

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en Yamanaka, Ryoken

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Tasaka, Ryo

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en Tasaka, Ryo

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Kohada, Yuki

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en Kohada, Yuki

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Miyamoto, Shunsuke

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en Miyamoto, Shunsuke

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Sekino, Yohei

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en Sekino, Yohei

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Kitano, Hiroyuki

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en Kitano, Hiroyuki

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Goto, Keisuke

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en Goto, Keisuke

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Ikeda, Kenichiro

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en Ikeda, Kenichiro

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Goriki, Akihiro

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en Goriki, Akihiro

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Hieda, Keisuke

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Kaminuma, Osamu

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Hinata, Nobuyuki

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en Hinata, Nobuyuki

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アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利情報
言語 en
権利情報 The final, published version of this article is available at https://doi.org/10.1159/000536539
権利情報
言語 en
権利情報 This is not the published version. Please cite only the published version.
権利情報
言語 ja
権利情報 この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。
主題
言語 en
主題Scheme Other
主題 Renal cell carcinoma
主題
言語 en
主題Scheme Other
主題 Nesprin1
主題
言語 en
主題Scheme Other
主題 SYNE1
主題
言語 en
主題Scheme Other
主題 Sunitinib
主題
言語 en
主題Scheme Other
主題 Tyrosine kinase inhibitor
内容記述
内容記述 Introduction: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). Methods: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and gene set enrichment analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC. Results: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells; however, it did not influence the proliferation of cells. RNA sequencing and gene set enrichment analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival. Conclusions: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment.
言語 en
出版者
出版者 Karger
言語 en
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
出版タイプ
出版タイプ AM
出版タイプResource http://purl.org/coar/version/c_ab4af688f83e57aa
関連情報
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 https://doi.org/10.1159/000536539
開始ページ
開始ページ 868
書誌情報 en : Oncology

巻 102, 号 10, p. 868-879, 発行日 2024-03-05
旧ID 55865
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