Differential gene expression in growth factors, epithelial mesenchymal transition and chemotaxis in the diffuse type compared with the intestinal type of gastric cancer

Introduction. The rapid development of basic science enabled us to significantly expand our understanding of various intercellular interactions. Epithelial-mesenchymal transition (EMT) is known to play a key role in certain tissue formation in the embryonic period. However, recent data show that EMT can also be observed in some pathological conditions, in particular, in various neoplasm development. This suggests that there are a number of alternative and fundamentally new mechanisms for the tumor formation and progression. Thus, EMT, which occurs in carcinomas, increases the invasiveness, immunoresistance, immunity to therapy, and the metastatic potential. Knowledge of EMT features and their timely recognition in morphological tumor diagnosis is of great predictive importance for patients. The aim of the research was to study the morphologi-cal features of epithelial-mesenchymal transition in the main types of gastric cancer. Materials and methods. We studied specimens of gastric carcinomas (N=64) including 31 cases of diffuse type, 19 cases of intestinal type, and 14 cases of mixed type. Results. All cases of the diffuse carcinoma group showed spread EMT features, which appeared already in the mucosa and completed with positive vimentin expression in 93.5% of cases. The malignant cell prolifera-tive activity was low; however, in 29% of cases we detected areas of moderate or even high activity. In the intestinal type gastric cancer, EMT developed as a result of tumor progression, it arose more often in the deeper layers and was incomplete and focal. As a rule, the proliferative activity of tumor cells was high and moderate. Vascular invasion occurred more often in diffuse type (90.3%), less often in mixed type (71.4%), and even less often in the intestine type (55.8%) gastric carcinoma. Conclusion. The variety of morphological features of EMT, its frequency, prevalence, completeness, and sequence in the development of various types of gastric cancer determines the features of their clinical manifestation and influences their further management. Keywords: gastric cancer, diagnosis, histological main types, EMT, morphopathology

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Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

International Journal of Oncology ◽

10.3892/ijo.2014.2387 ◽

2014 ◽

Vol 44 (6) ◽

pp. 1955-1970 ◽

Cited By ~ 19

Author(s):

SHIHORI TANABE ◽

KAZUHIKO AOYAGI ◽

HIROSHI YOKOZAKI ◽

HIROKI SASAKI

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Epithelial Mesenchymal Transition ◽

Diffuse Type ◽

Mesenchymal Transition ◽

Gene Expression Signatures ◽

Diffuse Type Gastric Cancer

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423 Differential gene expression pattern between preinvasive neoplasia and early invasive cervical carcinoma: putative mechanisms of angiogenesis and epithelial-mesenchymal transition involved in tumor invasion and metastasis

10.1136/ijgc-2020-igcs.367 ◽

2020 ◽

Author(s):

O Kurmyshkina ◽

P Kovchur ◽

T Volkova

Keyword(s):

Gene Expression ◽

Expression Pattern ◽

Differential Gene Expression ◽

Tumor Invasion ◽

Epithelial Mesenchymal Transition ◽

Gene Expression Pattern ◽

Invasion And Metastasis ◽

Invasive Cervical Carcinoma ◽

Mesenchymal Transition ◽

Differential Gene

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A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02329-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Wanting Song ◽

Yi Bai ◽

Jialin Zhu ◽

Fanxin Zeng ◽

Chunmeng Yang ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Risk Model ◽

Cox Regression ◽

Epithelial Mesenchymal Transition ◽

Risk Groups ◽

The Cancer Genome Atlas ◽

Critical Function ◽

Mesenchymal Transition ◽

Patient Prognosis

Abstract Background Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. Methods Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. Results Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. Conclusions We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

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Molecular Network Pathway Of ERBB In Diffuse-Type Gastric Cancer, Mesenchymal Stem Cells And Epithelial-Mesenchymal Transition

Journal of Clinical Epigenetics ◽

10.21767/2472-1158.100098 ◽

2018 ◽

Vol 04 (02) ◽

Cited By ~ 1

Author(s):

Shihori Tanabe

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Epithelial Mesenchymal Transition ◽

Molecular Network ◽

Diffuse Type ◽

Mesenchymal Transition ◽

Diffuse Type Gastric Cancer

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Hyperglycemia promotes Snail-induced epithelial–mesenchymal transition of gastric cancer via activating ENO1 expression

Cancer Cell International ◽

10.1186/s12935-019-1075-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 4

Author(s):

Xin Xu ◽

Bang Chen ◽

Shaopu Zhu ◽

Jiawei Zhang ◽

Xiaobo He ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Gastrointestinal Malignancies ◽

Mesenchymal Transition

Abstract Background Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. Emerging evidence indicates that hyperglycemia promotes tumor progression, especially the processes of migration, invasion and epithelial–mesenchymal transition (EMT). However, the underlying mechanisms of GC remain unclear. Method Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to detect the expression of glycolysis-related enzymes and EMT-related transcription factors. Small interfering RNA (siRNA) transfection was performed to decrease ENO1 expression. Immunohistochemistry (IHC), Western blot and qRT-PCR analyses were used to measure gene expression at the protein or mRNA level. CCK-8, wound-healing and Transwell assays were used to assess cell proliferation, migration and invasion. Results Among the glycolysis-related genes, ENO1 was the most significantly upregulated in GC, and its overexpression was correlated with poor prognosis. Hyperglycemia enhanced GC cell proliferation, migration and invasion. ENO1 expression was also upregulated with increasing glucose concentrations. Moreover, decreased ENO1 expression partially reversed the effect of high glucose on the GC malignant phenotype. Snail-induced EMT was promoted by hyperglycemia, and suppressed by ENO1 silencing. Moreover, ENO1 knockdown inhibited the activation of transforming growth factor β (TGF-β) signaling pathway in GC. Conclusions Our results indicated that hyperglycemia induced ENO1 expression to trigger Snail-induced EMT via the TGF-β/Smad signaling pathway in GC.

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Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer

Cancers ◽

10.3390/cancers12123833 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3833

Author(s):

Shihori Tanabe ◽

Sabina Quader ◽

Ryuichi Ono ◽

Horacio Cabral ◽

Kazuhiko Aoyagi ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Drug Resistance ◽

Signaling Pathways ◽

Pathway Analysis ◽

Rna Binding ◽

Binding Protein ◽

Diffuse Type ◽

Mesenchymal Transition ◽

Diffuse Type Gastric Cancer

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). A total of 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. Our analysis uncovered 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP), which have differences in gene expression between intestinal- and diffuse-type GC. A total of 463 direct relationships with three molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathway networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

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