Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma

Hidenari Hirata, Keishi Sugimachi, Yusuke Takahashi, Masami Ueda, Shotaro Sakimura, Ryutaro Uchi, Junji Kurashige, Yuki Takano, Sho Nanbara, Hisateru Komatsu, Tomoko Saito, Yoshiaki Shinden, Tomohiro Iguchi, Hidetoshi Eguchi, Kazushige Atsumi, Katsumi Sakamoto, Toshiro Doi, Masakazu Hirakawa, Hiroshi Honda, Koshi Mimori

Research output: Contribution to journalArticle

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Abstract

Background: Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC). Methods: The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated. Results: Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation. Conclusions: Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties.

Original languageEnglish
Pages (from-to)1402-1409
Number of pages8
JournalAnnals of Surgical Oncology
Volume22
DOIs
Publication statusPublished - Dec 1 2015

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Neoplastic Stem Cells
Homeobox Genes
Hepatocellular Carcinoma
Down-Regulation
Atlases
Genome
Fluorouracil
Survival
Neoplasms
Radiation Tolerance
Liver Neoplasms
Multivariate Analysis
Radiation

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma. / Hirata, Hidenari; Sugimachi, Keishi; Takahashi, Yusuke; Ueda, Masami; Sakimura, Shotaro; Uchi, Ryutaro; Kurashige, Junji; Takano, Yuki; Nanbara, Sho; Komatsu, Hisateru; Saito, Tomoko; Shinden, Yoshiaki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Atsumi, Kazushige; Sakamoto, Katsumi; Doi, Toshiro; Hirakawa, Masakazu; Honda, Hiroshi; Mimori, Koshi.

In: Annals of Surgical Oncology, Vol. 22, 01.12.2015, p. 1402-1409.

Research output: Contribution to journalArticle

Hirata, H, Sugimachi, K, Takahashi, Y, Ueda, M, Sakimura, S, Uchi, R, Kurashige, J, Takano, Y, Nanbara, S, Komatsu, H, Saito, T, Shinden, Y, Iguchi, T, Eguchi, H, Atsumi, K, Sakamoto, K, Doi, T, Hirakawa, M, Honda, H & Mimori, K 2015, 'Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma', Annals of Surgical Oncology, vol. 22, pp. 1402-1409. https://doi.org/10.1245/s10434-014-4242-0
Hirata, Hidenari ; Sugimachi, Keishi ; Takahashi, Yusuke ; Ueda, Masami ; Sakimura, Shotaro ; Uchi, Ryutaro ; Kurashige, Junji ; Takano, Yuki ; Nanbara, Sho ; Komatsu, Hisateru ; Saito, Tomoko ; Shinden, Yoshiaki ; Iguchi, Tomohiro ; Eguchi, Hidetoshi ; Atsumi, Kazushige ; Sakamoto, Katsumi ; Doi, Toshiro ; Hirakawa, Masakazu ; Honda, Hiroshi ; Mimori, Koshi. / Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma. In: Annals of Surgical Oncology. 2015 ; Vol. 22. pp. 1402-1409.
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abstract = "Background: Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC). Methods: The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated. Results: Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation. Conclusions: Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties.",
author = "Hidenari Hirata and Keishi Sugimachi and Yusuke Takahashi and Masami Ueda and Shotaro Sakimura and Ryutaro Uchi and Junji Kurashige and Yuki Takano and Sho Nanbara and Hisateru Komatsu and Tomoko Saito and Yoshiaki Shinden and Tomohiro Iguchi and Hidetoshi Eguchi and Kazushige Atsumi and Katsumi Sakamoto and Toshiro Doi and Masakazu Hirakawa and Hiroshi Honda and Koshi Mimori",
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T1 - Downregulation of PRRX1 Confers Cancer Stem Cell-Like Properties and Predicts Poor Prognosis in Hepatocellular Carcinoma

AU - Hirata, Hidenari

AU - Sugimachi, Keishi

AU - Takahashi, Yusuke

AU - Ueda, Masami

AU - Sakimura, Shotaro

AU - Uchi, Ryutaro

AU - Kurashige, Junji

AU - Takano, Yuki

AU - Nanbara, Sho

AU - Komatsu, Hisateru

AU - Saito, Tomoko

AU - Shinden, Yoshiaki

AU - Iguchi, Tomohiro

AU - Eguchi, Hidetoshi

AU - Atsumi, Kazushige

AU - Sakamoto, Katsumi

AU - Doi, Toshiro

AU - Hirakawa, Masakazu

AU - Honda, Hiroshi

AU - Mimori, Koshi

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC). Methods: The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated. Results: Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation. Conclusions: Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties.

AB - Background: Downregulation of paired related homeobox 1 (PRRX1) is associated with the acquisition of cancer stem cell (CSC)-like properties and poor prognosis in cancers. The purpose of this study is to clarify the role of PRRX1 expression in predicting prognosis and mediating CSC-like properties in hepatocellular carcinoma (HCC). Methods: The association between PRRX1 expression and overall survival (OS) of patients with HCC was analyzed in three independent datasets: 62 resected primary cases, 242 cases from GSE14520, and 162 cases from The Cancer Genome Atlas (TCGA). A cell line expressing PRRX1 (HuH7) was established for the functional analyses. The ability to form spheres, the expression levels of the hepatic CSC surface markers (CD13, CD133, and EpCAM), in vitro chemosensitivity to 5-fluorouracil (FU), and radiosensitivity were evaluated. Results: Univariate and multivariate analyses showed that the 5-year OS of the low PRRX1 expression group was significantly poorer than that of the high PRRX1 expression group (P = 0.024 and P = 0.045, respectively). Consistent with this, the low PRRX1 expression group in GSE14520 and TCGA datasets showed significantly shorter OS (P = 0.027 and P = 0.010, respectively). Gene set enrichment analysis on GSE14520 and TCGA datasets indicated that downregulation of PRRX1 was correlated with the stemness signature. The number of spheres and the expression levels of CSC markers were significantly decreased when PRRX1 was expressed. Moreover, PRRX1 impaired resistance to 5-FU and radiation. Conclusions: Downregulation of PRRX1 expression contributes to the poor prognosis of patients with HCC through acquisition of CSC-like properties.

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