The meta and bioinformatics analysis of GRP78 expression in gastric cancer

Zheng, Haixue; Gong, Baocheng; Zhao, Shuang

doi:10.18632/oncotarget.20318

Cited by 9 publications

(6 citation statements)

References 46 publications

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“…However, the relationship between BCAP31 and the development of NSCLC remains unclear. It has been reported that ER proteins can influence cell growth, migration, and invasion through epithelial-mesenchymal transition (EMT), ER stress, and autophagy [17][18][19] . We therefore hypothesized that BCAP31, as an ER chaperone, may play a role in NSCLC metastasis.…”

mentioning

confidence: 99%

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Wang

Jiang

et al. 2020

Sci Rep

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Non-small-cell lung cancer (NSCLC) represents most of lung cancers, is often diagnosed at an advanced metastatic stage. Therefore, exploring the mechanisms underlying metastasis is key to understanding the development of NSCLC. The expression of B cell receptor-associated protein 31 (BCAP31), calreticulin, glucose-regulated protein 78, and glucose-regulated protein 94 were analyzed using immunohistochemical staining of 360 NSCLC patients. It resulted that the high-level expression of the four proteins, but particularly BCAP31, predicted inferior overall survival. What's more, BCAP31 was closely associated with histological grade and p53 status, which was verified by seven cohorts of NSCLC transcript microarray datasets. Then, three NSCLC cell lines were transfected to observe behavior changes BCAP31 caused, we found the fluctuation of BCAP31 significantly influenced the migration, invasion of NSCLC cells. To identify the pathway utilized by BCAP31, Gene Set Enrichment Analysis was firstly performed, showing Akt/m-TOR/p70S6K pathway was the significant one, which was verified by immunofluorescence, kinase phosphorylation and cellular behavioral observations. Finally, the data of label-free mass spectroscopy implied that BCAP31 plays a role in a fundamental biological process. This study provides the first demonstration of BCAP31 as a novel prognostic factor related to metastasis and suggests a new therapeutic strategy for NSCLC.Lung cancer is one of the most prevalent neoplasms and the leading cause of cancer-related death worldwide, being responsible for nearly one in five cases 1 . Non-small-cell lung cancer (NSCLC) contributes to 85% of lung cancer cases. Owing to the absence of clinical symptoms and effective screening programs, most lung cancers are diagnosed at an advanced stage with metastasis. Targeted immunotherapy, including anti-angiogenic and checkpoint monoclonal antibodies or tyrosine kinase inhibitors, demonstrates better efficacy than traditional surgical treatment and radio-chemotherapy, although drug resistance and tumor heterogeneity remain significant problems, and metastasis remains the major cause of mortality 2 .It is therefore important to identify efficient symbolic markers of metastasis and therapeutic targets for NSCLC. Given the aberrant expression of specific genes in a variety of cancer types, restricted in testis or selected in normal tissue, cancer-testis antigens (CTAs) have emerged as efficient specific tumor targets which spare normal tissue from incurring damage during treatment 3 . Originally described in patients with malignant melanoma 4 , CTAs have been identified as biomarkers for a diverse range of cancers, including NSCLC 5 . Their expression is often coordinated 6 , and associated with poor clinical outcome 7 and advanced stage 8 , particularly metastasis 9 .with histological grade (p = 0.0009) and p53 status (p = 0.0058; Supplementary Table S1). However, there was no correlation between BCAP31 mRNA expression and NSCLC prognosis, which was inconsistent with our protein ...

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confidence: 99%

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Wang

Jiang

et al. 2020

Sci Rep

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“…In our study, tumour tissue with high IGFBP‐2 expression paired with low GRP78 expression were significantly associated with, a much shorter survival time (median = 4.0 months, p = 0.019). In other studies, higher GRP78 mRNA expression positively regulated overall and progression free survival in gastric cancer patients and was reported to be a positive marker for prognosis and chemotherapy response in breast cancer 39,40 . Moreover, drug induced GRP78 degradation in murine macrophages has been linked to prolonged ER stress and inflammation mediated by IL‐6 release, driving the tumorigenic microenvironment and cellular adaptation further exploiting adaptive mechanisms 41 …”

Section: Discussionmentioning

confidence: 94%

“…In other studies, higher GRP78 mRNA expression positively regulated overall and progression free survival in gastric cancer patients and was reported to be a positive marker for prognosis and chemotherapy response in breast cancer. 39,40 Moreover, drug induced GRP78 degradation in murine macrophages has been linked to prolonged ER stress and inflammation mediated by IL-6 release, driving the tumorigenic microenvironment and cellular adaptation further exploiting adaptive mechanisms. 41 The pleiotropic functions and spatiotemporal dynamics of IGFBP-2 and GRP78 appear to intricately shift in response to cellular context and adaptation.…”

Section: Discussionmentioning

confidence: 99%

Insulin‐like growth factor binding protein‐2 and glucose‐regulated protein 78 kDa: Potential biomarkers affect prognosis in IDH‐wildtype glioblastoma patients

et al. 2023

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Background:The overall survival of IDH-wildtype glioblastoma patients is poor despite best available treatments. There is an urgent need for new biomarkers to inform more precise disease stratification. Previous studies have identified insulin-like growth factor binding protein-2 (IGFBP-2) as a potential biomarker for glioblastoma diagnosis and therapeutic targeting. Other studies have indicated links between the insulin-like growth factor (IGF) axis and tumorigenic functions of a molecular chaperone glucose related protein of 78 kDa (GRP78). We aimed to interrogate the oncogenic effects of IGFBP-2 and GRP78 in our glioma stem cell (GSC) lines and clinical cohort. Methods:Immunoblotting, reverse transcription quantitative real-time PCR were used to quantify protein and mRNA levels derived from GSCs and nonmalignant neural stem cells (NSCs). Microarray analysis was used to compare the differences in IGFBP-2 (IGFBP-2) and GRP78 (HSPA5) transcript expression between NSCs, GSCs and adult human cortex samples. Immunohistochemistry was used to quantify IGFBP-2 and GRP78 expression in IDH-wildtype glioblastoma tissue sections (n = 92) and clinical implications assessed using survival analysis. Finally, the relationship between IGFBP-2 and GRP78 was further explored molecularly using coimmunoprecipitation.Results: Here, we demonstrate that IGFBP-2 and HSPA5 mRNA is overexpressed in GSCs and NSCs in comparison to non-malignant brain tissue. We also determined a relationship in which G144 and G26 GSCs expressed higher IGFBP-2 protein and mRNA than GRP78, and this was reversed in mRNA isolated from adult human cortex samples. Clinical cohort analysis revealed that Glioblastomas with high IGFBP-2 protein expression paired with low GRP78 protein expression were significantly associated with a much shorter survival time (Median = | 14427 HARLAND et al.

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“…Zheng et al demonstrated that GRP78 mRNA expression was higher in gastric cancer than normal tissues by performing bioinformatics analysis. Furthermore, a higher GRP78 mRNA expression was detectable both in intestinal-type carcinoma and diffuse-type counterpart in The Cancer Genome Atlas (TCGA) dataset [ 50 ]. GRP78 inhibition may possess potential benefits in clinical gastric cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation

et al. 2022

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Chemotherapy is the treatment of choice for gastric cancer; however, the currently available therapeutic drugs for treatment have limited efficacy. Cancer stemness and the tumor microenvironment may play crucial roles in tumor growth and chemoresistance. Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum chaperone facilitating protein folding and cell homeostasis during stress and may participate in chemoresistance. Isoliquiritigenin (ISL) is a bioactive flavonoid found in licorice. In this study, we demonstrated the role of GRP78 in gastric cancer stemness and evaluated GRP78-mediated stemness inhibition, tumor microenvironment regulation, and chemosensitivity promotion by ISL. ISL not only suppressed GRP78-mediated gastric cancer stem cell–like characteristics, stemness-related protein expression, and cancer-associated fibroblast activation but also gastric tumor growth in xenograft animal studies. The findings indicated that ISL is a promising candidate for clinical use in combination chemotherapy.

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The meta and bioinformatics analysis of GRP78 expression in gastric cancer

Cited by 9 publications

References 46 publications

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Insulin‐like growth factor binding protein‐2 and glucose‐regulated protein 78 kDa: Potential biomarkers affect prognosis in IDH‐wildtype glioblastoma patients

Isoliquiritigenin Inhibits Gastric Cancer Stemness, Modulates Tumor Microenvironment, and Suppresses Tumor Growth through Glucose-Regulated Protein 78 Downregulation

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