Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers

Abstract

Gastric cancer and liver cancer are among the most common malignancies and the leading causes of death worldwide, due to late detection and high recurrence rates. Today, these cancers have a heavy socioeconomic burden, for which a full understanding of their pathophysiological features is warranted to search for promising biomarkers and therapeutic targets. Osteopontin (OPN) is overexpressed in most patients with gastric and liver cancers. Over the past decade, emerging evidence has revealed a correlation of OPN level and clinicopathological features and prognosis in gastric and liver cancers, indicating its potential as an independent prognostic indicator in such patients. Functional studies have verified the potential of OPN knockdown as a therapeutic approach in vitro and in vivo. Furthermore, OPN mediates multifaceted roles in the interaction between cancer cells and the tumor microenvironment, in which many details need further exploration. OPN signaling results in various functions, including prevention of apoptosis, modulation of angiogenesis, malfunction of tumor-associated macrophages, degradation of extracellular matrix, activation of phosphoinositide 3-kinase-Akt and nuclear factor-κB pathways, which lead to tumor formation and progression, particularly in gastric and liver cancers. This editorial aims to review recent findings on alteration in OPN expression and its clinicopathological associations with tumor progression, its potential as a therapeutic target, and putative mechanisms in gastric and liver cancers. Better understanding of the implications of OPN in tumorigenesis might facilitate development of therapeutic regimens to benefit patients with these deadly malignancies.

Osteopontin, E-cadherin, and β-catenin expression as prognostic biomarkers in patients with radically resected gastric cancer

“…Available literature data suggested that osteopontin expression acts as a biomarker of clinical aggressiveness in patients with more advanced disease stage [9]. In our study, The p value is from the two-sided Wald test CI 95 % confidence interval of hazard ratio, COX-2 cyclooxygenase 2, HR hazard ratio, TNM tumor-node-metastasis…”

“…Functional E-cadherinb-catenin adhesion complexes are involved in anchorage mechanisms, and b-catenin is also involved in the Wingless/Wnt signaling pathway and transcription activation. Osteopontin, an integrin-binding glycophosphoprotein cytokine, plays an important role in cancer cell adhesion, protection from apoptosis, invasion, and migration [9] via the degradation of extracellular matrix, angiogenesis, and cell survival [10]. Literature data have documented that osteopontin expression is related to metastatic potential, and may be a prognostic marker in several tumor types, including GC, and especially in patients with more advanced disease stage [9].…”

“…Osteopontin, an integrin-binding glycophosphoprotein cytokine, plays an important role in cancer cell adhesion, protection from apoptosis, invasion, and migration [9] via the degradation of extracellular matrix, angiogenesis, and cell survival [10]. Literature data have documented that osteopontin expression is related to metastatic potential, and may be a prognostic marker in several tumor types, including GC, and especially in patients with more advanced disease stage [9]. Moreover, osteopontin and cyclooxygenase 2 (COX-2), which is one of the rate-limiting enzymes for prostaglandin synthesis, could synergistically induce angiogenesis and metastasis in GC [11].…”

The role of osteopontin expression in melanoma progression

“…In human malignant melanoma, OPN expression is significantly associated with reduced relapse-free survival and additional histological parameters that are associated with poor clinical outcome [7,24,29,33]. OPN is a prognostic marker in a variety of cancers [30,[39][40][41]. In metastatic and primary melanomas, OPN has also been suggested to be a novel promising biomarker for the detection of metastases in patients with primary melanomas [24,[42][43][44][45].…”

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

“…OPN, secreted by osteoblasts, osteoclasts, and osteocytes, is important in mineralization and bone resorption [9]. Recently, this protein was found to be relevant in regulation of immunity and inlammation, angiogenesis, oncogenesis, cancer progression, and apoptosis [10][11][12]. OPN interacts with most cells using two binding domains.…”