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) 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.

The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment

“…SPARC has been suggested as a prognostic biomarker for certain cancers such as soft tissue sarcoma, esophageal SCC and glioblastoma since its expression correlates with poor survival (232)(233)(234). In addition, SPP1 may be prognostic for breast, lung, gastric, liver and colon cancers since it associated with tumor progression and decreased patient survival (235)(236)(237)(238).…”

Pan-Cancer Analyses Reveal Prognostic Value of Osteomimicry Across 20 Solid Cancer Types

“…It was reported that SPP1 could regulate MMP-2 and MMP-9 expression and promote extracellular matrix degradation via activating αvβ-NF-κB pathway, and thus accelerate the growth, migration and invasion of cancer cells (Fong et al, 2009;Liu et al, 2010;Qin et al, 2018). Some studies also showed that SPP1 contributed to tumor cell migration, invasion and survival through PI3K-Akt (Fong et al, 2009;Zhang et al, 2014;Wei et al, 2018) and STAT3 (Behera et al, 2010) signaling, and could also promote tumor growth and metastasis by inducing angiogenesis (Dai et al, 2009;Wang et al, 2011). SPARC was a matricellular protein modulating cell-matrix interactions and was found up-regulated in tumor stroma and associated with poor prognosis in many cancer types, including colorectal cancer (Kurtul et al, 2017;Drev et al, 2019), pancreatic cancer (Vaz et al, 2015), cervical carcinoma (Shi et al, 2016), and non-small cell lung cancer (Koukourakis et al, 2003).…”

Identification and verification of 3 key genes associated with survival and prognosis of patients with colon adenocarcinoma via integrated bioinformatics analysis

“…Inhibition of SPP1 in the HCT116 cells consequently resulted in the suppression of cellular growth, migration, and invasion. SPP1 overexpression could thus enhance the proliferation, migration, and invasion of CRC cells as well as the activation of the PI3K pathway, accompanied by the increased expression of Snail and MMP9 [26]. As one of the transcription factors of EMT, snail can inhibit the expression of E-cadherin, thereby promotes the activation of EMT in tumor cells [27].…”

“…enrichments terms, including BP (71), MF(24), and CC(26). With regard to BP, DEGs were seen to be significantly enriched during cell adhesion, negative regulation of cell proliferation, angiogenesis, cytoskeleton organization, steroid hormonemediated signaling pathway, inflammatory response, negative regulation of protein kinase activity, and so on.…”