In vitro and clinical data analysis of Osteopontin as a prognostic indicator in colorectal cancer |
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| Authors: | Ran Wei Janet Pik Ching Wong Peng Lyu Xinping Xi Olivia Tong Shu‐Dong Zhang Hiu Fung Yuen Senji Shirasawa Hang Fai Kwok |
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| Institution: | 1. Faculty of Health Sciences, University of Macau, Taipa, Macau;2. Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, University of Ulster, Londonderry, UK;3. Institute of Molecular and Cell Biology, A*STAR, Singapore City, Singapore;4. Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan |
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| Abstract: | Osteopontin (OPN) has been shown to promote colorectal cancer (CRC) progression; however, the mechanism of OPN‐induced CRC progression is largely unknown. In this study, we found that OPN overexpression led to enhanced anchorage‐independent growth, cell migration and invasion in KRAS gene mutant cells but to a lesser 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 signature by connectivity mapping. In summary, OPN is a potential prognostic indicator and therapeutic target for colon cancer. |
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| Keywords: | colorectal cancer connectivity mapping Osteopontin survival |
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