Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma

Hisateru Komatsu, Tomohiro Iguchi, Takaaki Masuda, Hidenari Hirata, Masami Ueda, Shinya Kidogami, Yushi Ogawa, Kuniaki Sato, Qingjiang Hu, Sho Nambara, Tomoko Saito, Shotaro Sakimura, Ryutaro Uchi, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Background: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). Methods: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520. Gene set enrichment analysis (GSEA) was also conducted. Finally, knockdown experiments were performed using small interfering RNA (siRNA) in vitro. Results: In all cohorts, RND1 expression was decreased as cancer progressed, and was affected by promoter methylation. In our HCC cases, the 5-year overall survival (OS) and recurrence-free survival of patients with low RND1 expression was significantly poorer than those of patients with high RND1 expression. TCGA and GSE14520 analyses provided similar results for OS. Multivariate analysis indicated that RND1 expression was an independent prognostic factor for OS in all three cohorts. Additionally, GSEA showed an inverse correlation between RND1 expression and the Ras signaling activity. In vitro, knockdown of RND1 expression resulted in significant increases in proliferation, invasion, and chemoresistance to cisplatin in HCC cells. Conclusions: Reduced RND1 expression in HCC was associated with cancer progression, likely through regulation of the Ras signaling pathway, and may serve as a novel clinical biomarker for predicting prognosis in patients with HCC.

元の言語英語
ページ(範囲)850-859
ページ数10
ジャーナルAnnals of Surgical Oncology
24
発行部数3
DOI
出版物ステータス出版済み - 3 1 2017

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Hepatocellular Carcinoma
Phenotype
Survival
Atlases
Neoplasms
Genome
Genes
rho GTP-Binding Proteins
Methylation
Small Interfering RNA
Cisplatin
Multivariate Analysis
Biomarkers
Recurrence
Proteins
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

これを引用

Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma. / Komatsu, Hisateru; Iguchi, Tomohiro; Masuda, Takaaki; Hirata, Hidenari; Ueda, Masami; Kidogami, Shinya; Ogawa, Yushi; Sato, Kuniaki; Hu, Qingjiang; Nambara, Sho; Saito, Tomoko; Sakimura, Shotaro; Uchi, Ryutaro; Ito, Shuhei; Eguchi, Hidetoshi; Sugimachi, Keishi; Eguchi, Hidetoshi; Doki, Yuichiro; Mori, Masaki; Mimori, Koshi.

:: Annals of Surgical Oncology, 巻 24, 番号 3, 01.03.2017, p. 850-859.

研究成果: ジャーナルへの寄稿記事

Komatsu, H, Iguchi, T, Masuda, T, Hirata, H, Ueda, M, Kidogami, S, Ogawa, Y, Sato, K, Hu, Q, Nambara, S, Saito, T, Sakimura, S, Uchi, R, Ito, S, Eguchi, H, Sugimachi, K, Eguchi, H, Doki, Y, Mori, M & Mimori, K 2017, 'Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma', Annals of Surgical Oncology, 巻. 24, 番号 3, pp. 850-859. https://doi.org/10.1245/s10434-016-5573-9
Komatsu, Hisateru ; Iguchi, Tomohiro ; Masuda, Takaaki ; Hirata, Hidenari ; Ueda, Masami ; Kidogami, Shinya ; Ogawa, Yushi ; Sato, Kuniaki ; Hu, Qingjiang ; Nambara, Sho ; Saito, Tomoko ; Sakimura, Shotaro ; Uchi, Ryutaro ; Ito, Shuhei ; Eguchi, Hidetoshi ; Sugimachi, Keishi ; Eguchi, Hidetoshi ; Doki, Yuichiro ; Mori, Masaki ; Mimori, Koshi. / Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma. :: Annals of Surgical Oncology. 2017 ; 巻 24, 番号 3. pp. 850-859.
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title = "Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma",
abstract = "Background: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). Methods: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520. Gene set enrichment analysis (GSEA) was also conducted. Finally, knockdown experiments were performed using small interfering RNA (siRNA) in vitro. Results: In all cohorts, RND1 expression was decreased as cancer progressed, and was affected by promoter methylation. In our HCC cases, the 5-year overall survival (OS) and recurrence-free survival of patients with low RND1 expression was significantly poorer than those of patients with high RND1 expression. TCGA and GSE14520 analyses provided similar results for OS. Multivariate analysis indicated that RND1 expression was an independent prognostic factor for OS in all three cohorts. Additionally, GSEA showed an inverse correlation between RND1 expression and the Ras signaling activity. In vitro, knockdown of RND1 expression resulted in significant increases in proliferation, invasion, and chemoresistance to cisplatin in HCC cells. Conclusions: Reduced RND1 expression in HCC was associated with cancer progression, likely through regulation of the Ras signaling pathway, and may serve as a novel clinical biomarker for predicting prognosis in patients with HCC.",
author = "Hisateru Komatsu and Tomohiro Iguchi and Takaaki Masuda and Hidenari Hirata and Masami Ueda and Shinya Kidogami and Yushi Ogawa and Kuniaki Sato and Qingjiang Hu and Sho Nambara and Tomoko Saito and Shotaro Sakimura and Ryutaro Uchi and Shuhei Ito and Hidetoshi Eguchi and Keishi Sugimachi and Hidetoshi Eguchi and Yuichiro Doki and Masaki Mori and Koshi Mimori",
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doi = "10.1245/s10434-016-5573-9",
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TY - JOUR

T1 - Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma

AU - Komatsu, Hisateru

AU - Iguchi, Tomohiro

AU - Masuda, Takaaki

AU - Hirata, Hidenari

AU - Ueda, Masami

AU - Kidogami, Shinya

AU - Ogawa, Yushi

AU - Sato, Kuniaki

AU - Hu, Qingjiang

AU - Nambara, Sho

AU - Saito, Tomoko

AU - Sakimura, Shotaro

AU - Uchi, Ryutaro

AU - Ito, Shuhei

AU - Eguchi, Hidetoshi

AU - Sugimachi, Keishi

AU - Eguchi, Hidetoshi

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Mimori, Koshi

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Background: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). Methods: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520. Gene set enrichment analysis (GSEA) was also conducted. Finally, knockdown experiments were performed using small interfering RNA (siRNA) in vitro. Results: In all cohorts, RND1 expression was decreased as cancer progressed, and was affected by promoter methylation. In our HCC cases, the 5-year overall survival (OS) and recurrence-free survival of patients with low RND1 expression was significantly poorer than those of patients with high RND1 expression. TCGA and GSE14520 analyses provided similar results for OS. Multivariate analysis indicated that RND1 expression was an independent prognostic factor for OS in all three cohorts. Additionally, GSEA showed an inverse correlation between RND1 expression and the Ras signaling activity. In vitro, knockdown of RND1 expression resulted in significant increases in proliferation, invasion, and chemoresistance to cisplatin in HCC cells. Conclusions: Reduced RND1 expression in HCC was associated with cancer progression, likely through regulation of the Ras signaling pathway, and may serve as a novel clinical biomarker for predicting prognosis in patients with HCC.

AB - Background: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). Methods: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520. Gene set enrichment analysis (GSEA) was also conducted. Finally, knockdown experiments were performed using small interfering RNA (siRNA) in vitro. Results: In all cohorts, RND1 expression was decreased as cancer progressed, and was affected by promoter methylation. In our HCC cases, the 5-year overall survival (OS) and recurrence-free survival of patients with low RND1 expression was significantly poorer than those of patients with high RND1 expression. TCGA and GSE14520 analyses provided similar results for OS. Multivariate analysis indicated that RND1 expression was an independent prognostic factor for OS in all three cohorts. Additionally, GSEA showed an inverse correlation between RND1 expression and the Ras signaling activity. In vitro, knockdown of RND1 expression resulted in significant increases in proliferation, invasion, and chemoresistance to cisplatin in HCC cells. Conclusions: Reduced RND1 expression in HCC was associated with cancer progression, likely through regulation of the Ras signaling pathway, and may serve as a novel clinical biomarker for predicting prognosis in patients with HCC.

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U2 - 10.1245/s10434-016-5573-9

DO - 10.1245/s10434-016-5573-9

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VL - 24

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EP - 859

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

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