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

Abstract

A correlation between osteopontin, E-cadherin, b-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, b-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapsefree and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal b-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.

Prognostic significance of osteopontin expression in gastric cancer: a meta-analysis

“…Subsequently, seven studies were excluded because they lacked necessary information for meta-analysis. Finally, ten studies [14–23] published from 2007 to 2016 met the criteria for meta-analysis. The results of the search strategy were summarized in Figure 1.…”

“…Moreover, OPN was overexpressed in different solid tumors, including, but not limited to breast cancer [9], non-small cell lung cancer [10], colorectal cancer [11], hepatocellular carcinoma [12] and glioma [13]. Accumulated studies [14–23] also measured the OPN expression in primary tumor tissues or plasma in GC patients and investigated the clinical relevance between OPN and survival outcomes. However, the results of these studies were controversial and inconclusive.…”

Recombinant human bone morphogenetic protein-2 inhibits gastric cancer cell proliferation by inactivating Wnt signaling pathway via c-Myc with aurora kinases

“…The β-catenin signaling pathway is important for cancer progression, and the overexpression of β-catenin has been reported for various cancer types, including gastric cancer [22]. To further investigate the interaction between rhBMP-2 and the β-catenin signaling pathway, we measured the β-catenin protein levels after rhBMP-2 treatment using western blot.…”

Intracranial hypertension as the primary symptom of gastric signet-ring cell carcinoma

“…E-cadherin helps maintain cell polarity and characteristics, inhibits cell growth for regulation, and suppresses cancer invasion. [16] Abnormal E-cadherin expression often indicates advanced gastric cancer with a poor prognosis. [16] Human epidermal growth factor receptor-2 (HER2) is a member of the EGFR family, breast cancer patients who test positive for this receptor are generally expected to have a poor prognosis.…”

“…[16] Abnormal E-cadherin expression often indicates advanced gastric cancer with a poor prognosis. [16] Human epidermal growth factor receptor-2 (HER2) is a member of the EGFR family, breast cancer patients who test positive for this receptor are generally expected to have a poor prognosis. [17,18] Overexpression of HER2 in patients with gastric cancer ranges from 6% to 23%, [19,20] and its prognostic significance in gastric cancer is controversial.…”