Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer

Geng, Yiting; Chen, Xiaofeng; Qiu, Jiliang; Zhou, Yue; Wang, Jian; Liu, Lingxiang; Shao, Yongfeng; Yin, Yuan

doi:10.1007/s10147-013-0542-9

Cited by 21 publications

(15 citation statements)

References 33 publications

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“…Additionally, it has been reported that miR-7 and miR-331-3p are direct mediators of ERBB2 [23]. It was also reported that ERBB2 is highly expressed in GC tissues and is an independent negative prognostic factor for cancers [10], which is consistent with our study.…”

Section: Discussionsupporting

confidence: 92%

“…miR-495 regulates human epidermal growth factor receptor 2 (ERBB2) by binding to the 3′-untranslated regions (3′UTR) in connection with the target prediction program, microRNA.org. ERBB2, an oncogenic agent located in chromosome 17 (17q12–q21), encodes a 185-kDa transmembrane tyrosine kinase receptor (p185) [10]. ERBB2 has been identified to be implicated in cancerous initiation and progression, and its overexpression or amplification served as an independent prognostic factor in GC [11].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

Han

Zhou

et al. 2018

Med Sci Monit

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BackgroundIn recent years, the incidence of gastric cancer (GC) has been increasing worldwide. Emerging evidence shows that microRNAs (miRs) may be involved in the pathogenesis of GC. Thus, this study explored the mediatory role of miR-495 in GC chemosensitivity, and investigated the mechanism by which it affects the biological behaviors of GC cells via the mTOR signaling pathway.Material/MethodsAfter GC and paracancerous tissue collection, the positive rate of ERBB2 and mTOR was evaluated by immunohistochemistry. Subsequently, the expression of miR-495, ERBB2, and mTOR was determined by RT-qPCR and Western blot analysis. Next, the targeting relationship between miR-495 and ERBB2 was confirmed by dual-luciferase reporter gene assay. In addition, chemosensitivity and proliferation were detected by MTT assay and apoptosis was assessed by flow cytometry.ResultsWe found higher positive rates of ERBB2 and mTOR and decreased expression of miR-495 in GC tissues and showed that ERBB2 is the target gene of miR-495. Furthermore, we determined that overexpression of miR-495 and silencing of ERBB2 enhanced GC cell chemosensitivity and apoptosis, but inhibited GC cell proliferation. We also found that the effect of miR-495 inhibition was lost when ERBB2 was suppressed.ConclusionsThe key findings of our study demonstrate that the miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2. The study provides reliable evidence supporting the use of miR-495 as a novel potential target in the chemotherapy of GC.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

Han

Zhou

et al. 2018

Med Sci Monit

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“…A large body of evidence supports the central role of angiogenesis in GC development and progression but few data regarding the role of MCs in GC angiogenesis have been published [34,35,36]. In particular, in a study performed by Mukherjee et al [37], the authors studied MCs density in tissue from patients with gastric ulcers and in tissue from GC patients.…”

Section: Discussionmentioning

confidence: 99%

Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery

Ammendola

Sacco

Zuccalà

et al. 2016

IJMS

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Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage T2–3N2–3M0 (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson t-test analysis (r ranged from 0.74 to 0.79; p-value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies.

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“…In the eligible studies that did conduct ISH, the HER2 overexpression/gene amplification rates ranged from 2.0% to 18.3%, with an overall rate of 6.5% (3,11,14,16). In the present meta-analysis, HER2 IHC overexpression was not correlated with poor prognosis (HR 0.960, 95% CI 0.776-1.188) as in gastric cancer (22,23). However, CRC with HER2 IHC overexpression showed higher rates of lymph node and distant metastasis than CRC without HER2 IHC overexpression.…”

Section: Discussionmentioning

confidence: 51%

Clinicopathological Significance and Diagnostic Accuracy of HER2 Immunohistochemistry in Colorectal Cancer: A Meta-Analysis

2016

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Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer

Abstract: HER-2 was significantly overexpressed in gastric cancer versus normal tissue and correlated with VEGF expression. HER-2 in tumor or lymph nodes was an independent negative prognostic factor.

Cited by 21 publications

References 33 publications

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery

Clinicopathological Significance and Diagnostic Accuracy of HER2 Immunohistochemistry in Colorectal Cancer: A Meta-Analysis

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