Glucose-regulated protein 78 and heparanase expression in oral squamous cell carcinoma: correlations and prognostic significance

Abstract

BackgroundThe aim of the present study was to investigate the expression of glucose-related protein 78 (GRP78) and heparanase (HPA) in oral squamous cell carcinoma (OSCC) and their relationship with clinicopathological parameters and potential implications for survival.MethodsA total of 46 patients with OSCC and 10 normal individuals were recruited for the study. GRP78 and HPA expression were determined in the lesion tissues using immunohistochemical analysis. The correlation between GRP78 and HPA was assessed using the Spearman correlation analysis. The associations of GRP78 and HPA with clinicopathological characteristics and survival were examined using the x2-test, Kaplan–Meier, or Cox regression.ResultsPatients with OSCC showed a statistically significant higher prevalence of GRP78 and HPA expression than normal oral tissues. GRP78 and HPA expression was positively correlated with size, TNM stage, histological grade, lymphatic metastasis, and distant metastasis in OSCC patients. GRP78 expression was also positively correlated with HPA expression. Positive GRP78 and HPA expression was inversely correlated with survival in OSCC patients.ConclusionsHPA expression was found to be positively correlated with GRP78 expression. GRP78 and HPA are biomarkers that may have the potential to guide the treatment of oral cancer patients.

Expression of glucose regulated protein 78 (GRP78) determines colorectal cancer response to chemotherapy

“…It is well documented that GRP78 protein is expressed normally in the cell membrane of many cell types as GRP78 might act as a signal transduction receptor in the plasma membrane via the PI3K-Akt axis [21]. In cancer cells, the expression of GRP78 protein is extended to include cytoplasm, which is consistent with previous studies [22,23]. The increase in the cytoplas-mic expression of GRP78 in cancer cells is part of UPR pathway required for processing of misfolded proteins in the lumen of the ER that are accumulated during cancer progression.…”

Decreasing expression of glucose‐regulated protein GRP78/BiP as a significant prognostic predictor in patients with advanced laryngeal squamous cell carcinoma

“…In the present study, we attempted to clear up that confusion with respect to laryngeal SCC. GRP78/BiP has been observed to be elevated in the majority of solid tumors, and its high expression has been found to correlate with shorter survival, high pathological grade, aggressive phenotype, and poor prognosis . However, the upregulation of GRP78/BiP in lung cancer has been reported to be indicative of better prognosis; moreover, positive expression of GRP78/BiP in patients with neuroblastoma was closely associated with longer survival times .…”

“…Extensive expression of GRP78/BiP is found in many cancer cell lines and human neoplasms, and its expression is known to be closely associated with drug resistance, metastasis, tumor growth, survival, and resistance to chemotherapy . Several researchers have described that the expression level of GRP78/BiP plays an essential role in survival and tumor aggressiveness in patients with cancer, including lung cancer, breast cancer, prostate cancer, gastric cancer, and hepatocellular carcinoma . Of the patients with head and neck cancer, studies focused on the patients with oral SCC and found a close relationship between the expression level of GRP78/BiP and indicators of tumor progression, such as metastasis, disease stage, and survival .…”

“…In patients with gastric cancer, prostate cancer, renal cell carcinoma, and hepatocellular carcinoma, upregulation of GRP78/BiP is significantly related to poorer prognosis compared to downregulation of GRP78/BiP. However, the decreased expression of GRP78/BiP in patients with esophageal cancer and lung cancer yielded a poorer prognosis than the increased expression . However, the prognostic significance of GRP78/BiP in laryngeal SCC is still unclear.…”

“…3,4 Several researchers have described that the expression level of GRP78/BiP plays an essential role in survival and tumor aggressiveness in patients with cancer, including lung cancer, breast cancer, prostate cancer, gastric cancer, and hepatocellular carcinoma. [5][6][7][8][9][10][11][12] Of the patients with head and neck cancer, studies focused on the patients with oral SCC and found a close relationship between the expression level of GRP78/BiP and indicators of tumor progression, such as metastasis, disease stage, and survival. [5][6][7] In these reports, the elevated GRP78/BiP expression was shown to indicate increased tumor aggressiveness and reduced survival time, whereas decreased GRP78/BiP expression was significantly correlated with advanced disease stage and lymph node metastasis when compared to increased GRP78/BiP expression.…”