Glucose-Regulated Protein 78 Positivity as a Predictor of Poor Survival in Patients with Renal Cell Carcinoma

Kuroda, Kenji; Horiguchi, Akio; Ito, Keiichi; Asakuma, Junichi; Sato, Akinori; Yoshii, Hidehiko; Hayakawa, Masamichi; Sumitomo, Makoto; Asano, Tomohiko

doi:10.1159/000330883

Cited by 25 publications

(20 citation statements)

References 36 publications

(22 reference statements)

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“…Another previous study, which analyzed 137 renal cell carcinoma specimens, established that there was a significant association between GRP78 positivity and a higher tumor grade, an advanced T stage, lymphovascular invasion, regional nodal involvement and distant metastases (27). In the present study, despite the association between GRP78 and osteosarcoma grade, a correlation with the T stage was not detected.…”

Section: Tumor Tissue -----------------------------------------------contrasting

confidence: 87%

Expression and significance of glucose-regulated protein 78 in human osteosarcoma

Zhang

Wang

et al. 2015

Oncology Letters

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Abstract. The present study aimed to investigate the expression of glucose-regulated protein 78 (GRP78) in osteosarcoma cells, and analyze the differences in expression between tumor and normal tissues, pre-and post-chemotherapy patients and metastatic and non-metastatic tumors. According to these results, the associations between the expression of GRP78 and tumor growth, metastasis and chemotherapeutics could be determined. Between 2007 and 2012, 60 patients who had been diagnosed with osteosarcoma were selected for the present study. Of these patients, 20 presented with non-metastatic tumors and 40 with metastatic tumors, and 20 had been treated without chemotherapy and 40 with chemotherapy. In addition, 60 specimens obtained from adjacent normal tissues were collected for the control groups. Immunofluorescence staining was used to examine the expression of GRP78 in the different tissues. The total RNA and protein were extracted from crushed tissues and used in the reverse transcription polymerase chain reaction and western blot analysis. GRP78 was primarily located in the intracavity of the endoplasmic reticulum. The expression level of GRP78 in the tumor tissue was higher than that in the normal tissue surrounding the tumor (P<0.01). In addition, the level was higher in the metastatic tumors compared with the non-metastatic tumors (P<0.05), and in the non-chemotherapy-treated patients compared with the chemotherapy-treated patients (P<0.01). The expression level of GRP78 mRNA in the tumor tissue was higher than that in the normal tissue (P<0.01). Furthermore, the level was higher in the metastasis group than in the non-metastasis group (P<0.05), and in the non-chemotherapy group than in the chemotherapy group (P<0.01). The expression level of GRP78 protein was higher in the tumor tissue compared with the normal tissue (P<0.01), in the metastasis group compared with the non-metastasis group (P<0.05), and in the non-chemotherapy group compared with the chemotherapy group (P<0.01). In conclusion, the present study detected the expression of GRP78 in patients with osteosarcoma and revealed a higher expression level in the tumor tissues compared with the normal tissues around the tumor, in the metastasis group compared with the non-metastasis group and in the non-chemotherapy-treated group compared with the chemotherapy-treated group.

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Section: Tumor Tissue -----------------------------------------------contrasting

confidence: 87%

Expression and significance of glucose-regulated protein 78 in human osteosarcoma

Zhang

Wang

et al. 2015

Oncology Letters

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“…GRP78, a marker of ER stress, has been reported to be up-regulated in RCC and to be involved in the growth of RENCA renal carcinoma cells [23, 24, 30]. To explore whether the anti-tumor function of miR-30a-5p in ccRCC is mediated by modulating the expression of GRP78, we initially analyzed the GRP78 expression pattern in ccRCC tissues and RCC cell lines.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

Wang

Cai

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: MiR-30a-5p, a member of the microRNA-30 family (miR-30), is known to function as a tumor suppressor in several different cancers. However, the expression levels, biological function, and underlying mechanisms of miR-30a-5p in renal cell carcinoma (RCC) remain unclear. Glucose-regulated protein78 (GRP78) is a common cancer biomarker and promotes the growth and survival of cancer cells. The expression of GRP78 has been reported to be modulated by miR-30a in neurons. In this study, the expression profile of miR-30a-5p in clear cell renal cell carcinoma (ccRCC) and its effect on ccRCC through regulating GRP78 expression was investigated. Methods: MiR-30a-5p expression was analyzed using bioinformatic software on open microarray datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and confirmed by quantitative RT-PCR (qRT-PCR) in ccRCC cell lines. Cell proliferation was investigated using CCK-8 and cell count assays. Western blotting, immunohistochemistry, luciferase reporter assays, and flow cytometry were employed to investigate the mechanisms of the effect of miR-30a-5p on ccRCC Results: MiR-30a-5p was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. MiR-30a-5p was found to both suppress the growth of ccRCC cells and promote apoptosis of ccRCC cells in vitro. GRP78 was the direct target gene of miR-30a-5p, and the GRP78 expression was inversely correlated with the expression of miR-30a-5p in vivo and in vitro. The functional studies of GRP78 overexpression or knockdown demonstrated that GRP78 promoted proliferation and anti-apoptosis of ccRCC cells, and the oncogenic activity of GRP78 resulting in by miR-30a-5p overexpression. Conclusion: MiR-30a-5p is a bona fide negative regulator of GRP78 expression, and the anti-tumor activity of miR-30a-5p in ccRCC is due at least in part to down-regulating GRP78 expression and modulating the unfolded protein response (UPR) pathway. Thus, miR-30-GRP78 interaction provides a novel therapeutic candidate target in ccRCC treatment.

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“…Some molecules markers, such as CAIX (carbonic anhydrase IX), VEGF (vascular endothelial growth factor), GRP78 (glucose-regulated protein 78), CD146 had been found to be a powerful marker for the prognosis of RCC [15,16,17,18]. Circulating cfDNA, a biomarker that is easily accessible and preferably noninvasive, has been shown to have diagnostic and prognostic potential in RCC [12,19].…”

Section: Discussionmentioning

confidence: 99%

Monitoring of Plasma Cell-Free DNA in Predicting Postoperative Recurrence of Clear Cell Renal Cell Carcinoma

Wan

Zhu

Jiang³

et al. 2013

Urol Int

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Background: Circulating cell-free DNA (cfDNA) mostly originates from tumors and its level correlates with treatment. We assessed whether the level of plasma cfDNA could help monitor recurrence after nephrectomy. Methods: This study included 92 patients with clear cell renal cell carcinoma (cRCC). Quantitative real-time PCR was used to measure the level of plasma cfDNA before and after nephrectomy. Results: The pretreatment level of plasma cfDNA in patients with metastatic cRCC (6.04 ± 0.72) was significantly higher than in those with localized cRCC (5.29 ± 0.53, p = 0.017) or controls (0.65 ± 0.29, p < 0.001). Of patients with localized cRCC, those with recurrence had a significantly higher plasma cfDNA level than those without (p = 0.024). The patients with a high plasma cfDNA level had a significantly higher recurrence rate than those with a low plasma cfDNA level before and after nephrectomy (p = 0.018). Conclusion: The level of plasma cfDNA may be useful as a tool to monitor patients during follow-up and guide further diagnostic work-up for the detection of recurrence.

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Glucose-Regulated Protein 78 Positivity as a Predictor of Poor Survival in Patients with Renal Cell Carcinoma

Cited by 25 publications

References 36 publications

Expression and significance of glucose-regulated protein 78 in human osteosarcoma

Expression and significance of glucose-regulated protein 78 in human osteosarcoma

MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78 Expression

Monitoring of Plasma Cell-Free DNA in Predicting Postoperative Recurrence of Clear Cell Renal Cell Carcinoma

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