Correlations of Human Epithelial Growth Factor Receptor 2 Overexpression with MUC2, MUC5AC, MUC6, p53, and Clinicopathological Characteristics in Gastric Cancer Patients with Curative Resection

Park, Kwang Kuk; Yang, Song I; Seo, Kyung Won; Yoon, Ki Hyun; Lee, Sang Ho; Jang, Hee Kyung; Shin, Yeon Myeong

doi:10.1155/2015/946359

Cited by 8 publications

(7 citation statements)

References 61 publications

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“…Gastric mucosal barrier protects gastric mucosa from hydrochloric acid and various harmful substances. MUC5AC is a gel-formed mucin, which is known as the main component of the gastric mucus layer [20][21][22][23][24][25][26]. MUC5AC is a wellknown marker of gastric differentiation, which is considered to be a very important prognostic indicator of GC and is often used in clinical evaluation [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

Yang¹

2020

Med Oncol

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Gastric cancer (GC) is one of the most common malignant tumors in the world, and it is also the third largest cause of cancerrelated death in the world. As far as we know, no biomarker has been widely accepted for early diagnosis and prognosis prediction of gastric cancer. The purpose of this study is to find potential biomarkers to predict the prognosis of GC. The gene expression profiles of GSE2685 were downloaded from GEO database. Morpheus was used to calculate the differentially expressed genes (DEGs) between primary advanced gastric cancer tissues and noncancerous gastric tissues. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and protein-protein interaction (PPI) network of DEGs was constructed. Kaplan-Meier Plotter was used to determine the overall survival (OS) outcomes of UC5AC, MUC1, KRT7, GAPDH, CD44, and GEPIA was used to determine the Pearson correlation analysis. In total, 710 DEGs were identified in GC, including 396 upregulated genes and 314 downregulated genes. GO enrichment revealed that they were mainly enriched in binding, catalytic activity, cellular process and cell. KEGG pathway revealed that they were mainly enriched in metabolic pathways, pathways in cancer and PI3K-Akt signaling pathway. MUC5AC, MUC1, KRT7, GAPDH, CD44 were identified from the PPI network. MUC5AC, MUC1, KRT7, GAPDH, CD44 were demonstrated to have prognostic value for patients with GC. MUC5AC, MUC1 exhibited low expression levels in GC tissues, KRT7, GAPDH, CD44 presented high expression levels in GC tissues. In particular, KRT7 is hardly expressed in normal gastric tissues. MUC5AC and MUC1 were negatively correlated with GAPDH, CD44, respectively; and GAPDH was positively correlated with CD44 and KRT7, respectively. Moreover. MUC5AC, MUC1, KRT7, GAPDH, and CD44 are not only related to GC but also to apoptosis pathway. Results from the present study suggested that MUC5AC, MUC1, KRT7, GAPDH, CD44 may represent novel prognostic biomarkers for GC.

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Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

Yang¹

2020

Med Oncol

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“…For the first time, as per our knowledge, the methylation of MUC6 promoter region was shown to cause a significant downregulation of MUC6 in GC and that the downregulation of MUC6 may promote the metastasis of GC. Earlier studies focused on detecting the expression of MUC6 in GC and normal tissues [6] . A decrease in MUC6 expression in GC has been elucidated [9,19] , and MUC6 gene polymorphism appears to be associated with the tendency of GC [20] .…”

Section: Discussionmentioning

confidence: 99%

“…MUC6 is known to be a marker of gastric foveolar and antral mucous glandular cells, reflecting gastric phenotypes and acts as a significant physiological barrier against various aggressions of the underlying epithelia [5] . It is also reported to be significantly correlated with epithelial growth factor receptor 2, which is related to the invasive behavior of gastric cancer (GC) [6] . Nevertheless, MUC6 is a relatively less-investigated molecule; thus, not much is documented about its expressional changes in GC, the mechanism of such changes, and the effect of these changes on the metastasis of GC.…”

Section: Introductionmentioning

confidence: 99%

Methylation regulation of MUC6 correlates with metastasis of gastric cancer

Shi

2020

Preprint

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Background: The aim of this study was to investigate the mechanism of the downregulation of MUC6 and its influence on GC metastasis.Methods: The expression of MUC6 was examined in cancer tissues and their corresponding adjacent normal tissues in 40 gastric adenocarcinoma patients. The investigation of methylation level of MUC6 promoter region in gastric cell lines and gastric specimen tissues was performed through immunohistochemistry and/or quantitative polymerase chain reaction (qPCR)s. MUC6 was knocked down in GES-1 cell lines and overexpressed in SGC7901 cell lines; the effects of MUC6 knockdown and overexpression on cell migration and invasion were examined using Transwell migration assay. The effects of demethylation and methylation on MUC6 expression were examined using Western blot, qPCR, or double luciferase report experiment.Results: The expression of MUC6 in GC tissues was significantly lower than that in normal paracancerous tissues. While the cells migration and invasion abilities were decreased significantly after overexpression of MUC6, these abilities increased significantly after the knocking down of MUC6. The methylation levels of MUC6 in GC tissues and GC cell lines (MGC803, MKN45, AGS, SGC7901, and BGC823) were significantly higher than those in paracancerous tissues and gastric epithelial cells. The promoter methylation could significantly reduce the binding of MUC6 promoter region to the related transcription factors. The expression of MUC6 increased with the concentration of demethylated drugs and the time of action.Conclusion: The expression of MUC6 was regulated by methylation of its promoter, and this methylation of MUC6 promoter may lead to significant downregulation of MUC6 in GC and promote the metastasis of GC.

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“…an independent poor prognostic factor in gastric carcinoma and that Her-2 overexpression was found to be associated with several clinicopathological characteristics related to the invasive behavior of gastric cancer, especially depth of invasion, lymph node metastasis, and lymphatic invasion (Park et al, 2015;Yan et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Expression of CDX-2 and ALK in primary gastric carcinoma

Abd-Elazeem¹,

Radi²

2015

Egyptian Journal of Pathology

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Background Gastric carcinoma still represents a serious health problem. Prognostic biomarkers that predict the disease outcome and aid in better treatment options are of great value. Intestinal differentiation marker, caudal type homeobox-2 (CDX-2), and tumorigenic marker, anaplastic lymphoma kinase (ALK), may have influence on tumor behavior and prognosis.Aim The aim of this study was to analyze the expression of CDX-2 and ALK in relation to Her-2 status and clinicopathological factors of gastric carcinoma to assess the prognostic significance of combined biomarkers expression.Materials and methods Immunohistochemical expression of CDX-2 and ALK was studied in 68 paraffinembedded specimens of primary gastric carcinoma.Results CDX-2 and ALK expressions were detected in 58.5 and 11.8% of studied cases, respectively. CDX-2 expression was significant in intestinal type tumors (P = 0.0001). A significant negative correlation was found between CDX-2 expression and tumor differentiation (P = 0.003), pT stage (P = 0.0001), lymph node metastasis (P = 0.005), and Her-2 expression (P = 0.042), whereas ALK expression was significantly more in diffuse type (P = 0.023). A significant positive correlation was observed between ALK-positive tumors and degree of tumor differentiation (P = 0.006), lymph node metastasis (P = 0.011), and Her-2 expression (P = 0.029). A significant negative relation was detected between CDX-2 and ALK expressions (P = 0.039).Conclusion Combined expressions of CDX-2 and ALK in gastric carcinoma allow the classification of patients into groups with different prognosis, clinical outcomes, and treatment options. CDX-2 + /ALK -cases were significantly associated with favorable prognostic factors. Egypt J Pathol 35:150-156 c

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Correlations of Human Epithelial Growth Factor Receptor 2 Overexpression with MUC2, MUC5AC, MUC6, p53, and Clinicopathological Characteristics in Gastric Cancer Patients with Curative Resection

Cited by 8 publications

References 61 publications

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer

Methylation regulation of MUC6 correlates with metastasis of gastric cancer

Expression of CDX-2 and ALK in primary gastric carcinoma

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