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

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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.
Original languageEnglish
JournalJournal of Cellular and Molecular Medicine
Early online date30 May 2018
DOIs
Publication statusE-pub ahead of print - 30 May 2018

Keywords

  • Colorectal Cancer
  • survival
  • Osteopontin
  • Connectivity mapping

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