In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer

Ran Wei, Janet Pik Ching Wong, Peng Lyu, Xinping Xi, Olivia L.H. Tong, Shu-Dong Zhang, Hiu‑Fung Yuen, Senji Shirasawa, Hang Fai Kwok

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progres- sion; however, the mechanism of OPN-induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage-inde- pendent growth, cell migration and invasion in KRAS gene mutant cells but to a les- ser extent in KRAS wild-type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E-cadherin in KRAS mutant cells. In human CRC specimens, a high- level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E-cadherin expression. Furthermore, we have found that 15 genes were co-upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene sig- nature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.
LanguageEnglish
JournalJournal of Cellular and Molecular Medicine
Early online date30 May 2018
DOIs
Publication statusE-pub ahead of print - 30 May 2018

Fingerprint

Osteopontin
Colorectal Neoplasms
Metalloproteases
Cadherins
Genes
In Vitro Techniques
Phosphatidylinositol 3-Kinases
Colonic Neoplasms
Cell Movement
Survival

Keywords

  • Colorectal Cancer
  • survival
  • Osteopontin
  • Connectivity mapping

Cite this

Wei, Ran ; Wong, Janet Pik Ching ; Lyu, Peng ; Xi, Xinping ; Tong, Olivia L.H. ; Zhang, Shu-Dong ; Yuen, Hiu‑Fung ; Shirasawa, Senji ; Kwok, Hang Fai. / In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer. In: Journal of Cellular and Molecular Medicine. 2018.
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title = "In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer",
abstract = "Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progres- sion; however, the mechanism of OPN-induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage-inde- pendent growth, cell migration and invasion in KRAS gene mutant cells but to a les- ser extent in KRAS wild-type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E-cadherin in KRAS mutant cells. In human CRC specimens, a high- level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E-cadherin expression. Furthermore, we have found that 15 genes were co-upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene sig- nature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.",
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author = "Ran Wei and Wong, {Janet Pik Ching} and Peng Lyu and Xinping Xi and Tong, {Olivia L.H.} and Shu-Dong Zhang and Hiu‑Fung Yuen and Senji Shirasawa and Kwok, {Hang Fai}",
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In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer. / Wei, Ran; Wong, Janet Pik Ching; Lyu, Peng; Xi, Xinping; Tong, Olivia L.H.; Zhang, Shu-Dong; Yuen, Hiu‑Fung; Shirasawa, Senji; Kwok, Hang Fai.

In: Journal of Cellular and Molecular Medicine, 30.05.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer

AU - Wei, Ran

AU - Wong, Janet Pik Ching

AU - Lyu, Peng

AU - Xi, Xinping

AU - Tong, Olivia L.H.

AU - Zhang, Shu-Dong

AU - Yuen, Hiu‑Fung

AU - Shirasawa, Senji

AU - Kwok, Hang Fai

PY - 2018/5/30

Y1 - 2018/5/30

N2 - Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progres- sion; however, the mechanism of OPN-induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage-inde- pendent growth, cell migration and invasion in KRAS gene mutant cells but to a les- ser extent in KRAS wild-type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E-cadherin in KRAS mutant cells. In human CRC specimens, a high- level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E-cadherin expression. Furthermore, we have found that 15 genes were co-upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene sig- nature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.

AB - Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progres- sion; however, the mechanism of OPN-induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage-inde- pendent growth, cell migration and invasion in KRAS gene mutant cells but to a les- ser extent in KRAS wild-type cells. OPN overexpression also induced PI3K signalling, expression of Snail and Matrix metallopeptidase 9 (MMP9), and suppressed the expression of E-cadherin in KRAS mutant cells. In human CRC specimens, a high- level expression of OPN significantly predicted poorer survival in CRC patients and OPN expression was positively correlated with MMP9 expression, and negatively correlated with E-cadherin expression. Furthermore, we have found that 15 genes were co-upregulated in OPN highly expression CRC and a list of candidate drugs that may have potential to reverse the secreted phosphoprotein 1 (SPP1) gene sig- nature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer.

KW - Colorectal Cancer

KW - survival

KW - Osteopontin

KW - Connectivity mapping

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