scholarly journals HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Marta Smolińska ◽  
Dariusz Grzanka ◽  
Paulina Antosik ◽  
Anna Kasperska ◽  
Izabela Neska-Długosz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Statistical Significance ◽  
Expression Patterns ◽  
Clinical Information ◽  
Tissue Microarrays ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Satb1 Expression

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.

scholarly journals Transcriptional and Epigenetic Bioinformatic Analysis of Claudin-9 Regulation in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Elizabeth Hernández-Nava ◽  
Luis F. Montaño ◽  
Erika P. Rendón-Huerta
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Biological Significance ◽  
Gene Promoter ◽  
Promoter Sequence ◽  
Data Bank ◽  
Bioinformatic Analysis ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
New Genes

Gastric cancer is a heterogeneous disease that represents 5% to 10% of all new cancer cases worldwide. Advances in histological diagnosis and the discovery of new genes have admitted new genomic classifications. Nevertheless, the bioinformatic analysis of gastric cancer databases has favored the detection of specific differentially expressed genes with biological significance. Claudins, a family of proteins involved in tight junction physiology, have emerged as the key regulators of cellular processes, such as growth, proliferation, and migration, associated with cancer progression. The expression of Claudin-9 in the gastric cancer tissue has been linked to poor prognosis, however, its transcriptional and epigenetic regulations demand a more comprehensive analysis. Using the neural network promoter prediction, TransFact, Uniprot-KB, Expasy-SOPMA, protein data bank, proteomics DB, Interpro, BioGRID, String, and the FASTA protein sequence databases and software, we found the following: (1) the promoter sequence has an unconventional structure, including different transcriptional regulation elements distributed throughout it, (2) GATA 4, GATA 6, and KLF5 are the key regulators of Claudin-9 expression, (3) Oct1, NF-κB, AP-1, c-Ets-1, and HNF-3β have the higher binding affinity to the CLDN9 promoter, (4) Claudin-9 interacts with cell differentiation and development proteins, (5) CLDN9 is highly methylated, and (6) Claudin-9 expression is associated with poor survival. In conclusion, Claudin-9 is a protein that should be considered a diagnostic marker as its gene promoter region binds to the transcription factors associated with the deregulation of cell control, enhanced cell proliferation, and metastasis.

scholarly journals S100P is a molecular determinant of E-cadherin function in gastric cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Patrícia Carneiro ◽  
Ana Margarida Moreira ◽  
Joana Figueiredo ◽  
Rita Barros ◽  
Patrícia Oliveira ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Data Mining Approach ◽  
Molecular Determinant ◽  
Gastric Cancer Patients ◽  
And Function ◽  
E Cadherin

Abstract Background E-cadherin has been awarded a key role in the aetiology of both sporadic and hereditary forms of gastric cancer. In this study, we aimed to identify molecular interactors that influence the expression and function of E-cadherin associated to cancer. Methods A data mining approach was used to predict stomach-specific candidate genes, uncovering S100P as a key candidate. The role of S100P was evaluated through in vitro functional assays and its expression was studied in a gastric cancer tissue microarray (TMA). Results S100P was found to contribute to a cancer pathway dependent on the context of E-cadherin function. In particular, we demonstrated that S100P acts as an E-cadherin positive regulator in a wild-type E-cadherin context, and its inhibition results in decreased E-cadherin expression and function. In contrast, S100P is likely to be a pro-survival factor in gastric cancer cells with loss of functional E-cadherin, contributing to an oncogenic molecular program. Moreover, expression analysis in a gastric cancer TMA revealed that S100P expression impacts negatively among patients bearing Ecad− tumours, despite not being significantly associated with overall survival on its own. Conclusions We propose that S100P has a dual role in gastric cancer, acting as an oncogenic factor in the context of E-cadherin loss and as a tumour suppressor in a functional E-cadherin setting. The discovery of antagonist effects of S100P in different E-cadherin contexts will aid in the stratification of gastric cancer patients who may benefit from S100P-targeted therapies. Graphical abstract

scholarly journals Upregulation of long noncoding RNA SNHG1 indicates a poor prognosis in patients with gastric cancer

2020 ◽  
Vol 18 ◽  
pp. 205873922094614
Author(s):  
Hua-Li Zhu ◽  
Jing Zou
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Poor Prognosis ◽  
The Cancer Genome Atlas ◽  
Clinicopathological Parameters ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Expression Levels

It is indicated that the dysregulation of long noncoding RNAs (lncRNAs) is implicated in cancer progression. However, the clinical significance of lncRNA small nucleolar RNA host gene 1 (SNHG1) in gastric cancer remains elusive. The expression levels of SNHGs and the association of SNHG1/10/11 with the clinical characteristics in patients with gastric cancer were analyzed by The Cancer Genome Atlas RNA-seq data. A Cox proportional hazard regression model was used to evaluate the association of SNHG1/10/11 expression with the clinical outcomes in patients with gastric cancer. It was demonstrated that SNHG1/10/11 expression levels were dramatically elevated in gastric cancer tissue samples as compared with the adjacent normal tissues. Increased expression of SNHG1 had no correlation with the clinicopathological parameters, but acted as an independent prognostic factor of poor survival (hazard ration (HR) = 0.590, 95% confidence interval (CI) = 0.399–0.872, P = 0.008) and tumor recurrence (HR = 2.457, 95% CI = 1.442–4.186, P = 0.001) in patients with gastric cancer. In addition, knockdown of SNHG1 in vitro inhibited the proliferation and invasion of gastric cancer cells. Our findings showed that the upregulation of lncRNA SNHG1 indicated a poor prognosis in patients with gastric cancer and might offer a promising therapeutic target for gastric cancer.

scholarly journals BUBR1 Insufficiency Is Correlated with eNOS Reduction Experimentally In Vitro and In Vivo, and in Gastric Cancer Tissue

2018 ◽  
Vol 38 (11) ◽  
pp. 6099-6106 ◽  
Author(s):  
EISUKE KAWAKUBO ◽  
TAKUYA MATSUMOTO ◽  
KEIJI YOSHIYA ◽  
SHO YAMASHITA ◽  
TOMOKO JOGO ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue

scholarly journals Deficiency of microRNA-628-5p promotes the progression of gastric cancer by upregulating PIN1

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Yang Chen ◽  
Yaran Wu ◽  
Shuhui Yu ◽  
Hongying Yang ◽  
Xiya Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Gastric Cancer Tissue ◽  
Primary Site ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Common Cancer ◽  
Exogenous Expression ◽  
Gastric Cancer Progression ◽  
Related Mortality

Abstract Gastric cancer is one of the most common cancer and is the second leading cause of cancer-related mortality in the world. PIN1, belonging to peptidyl-prolyl cis-trans isomerase family, uniquely catalyzes the structural transformation of phosphorylated Ser/Thr-Pro motif. It’s high expressed in most cancers and promotes their progression. However, the mechanism of PIN1 high expression and its function in gastric cancer progression are still unclear. In this research, we revealed that PIN1 not only promotes the proliferation and colony formation of gastric cancer, but also increases its migration and invasion. The PIN1 expression in metastasis lesion is usually higher than the corresponding primary site. Inhibiting PIN1 by shRNA suppresses the progression of gastric cancer significantly. Besides, we demonstrated that miR-628-5p is a novel PIN1-targeted microRNA, and the expression of miR-628-5p is negatively correlated with PIN1 in gastric cancer. Exogenous expression of miR-628-5p inhibits the progression of gastric cancer that revered by restoring PIN1 expression. However, miR-628-5p is downregulated in majority of gastric cancer tissue especially in metastasis lesion. The lower miR-628-5p level indicates poorer prognosis. In summary, our study demonstrated that deficient miR-628-5p expression facilitates the expression of PIN1, and consequently promotes the progression of gastric cancer.

scholarly journals Analysis of SEMA3B methylation and expression patterns in gastric cancer tissue and cell lines

2014 ◽  
Vol 31 (3) ◽  
pp. 1211-1218 ◽  
Author(s):  
RENPIN CHEN ◽  
XIAOJU ZHUGE ◽  
ZHIMING HUANG ◽  
DEYI LU ◽  
XIAOHUA YE ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Expression Patterns ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue

scholarly journals Tenascin-c knockdown suppresses vasculogenic mimicry of gastric cancer by inhibiting ERK- triggered EMT

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Xing Kang ◽  
En Xu ◽  
Xingzhou Wang ◽  
Lulu Qian ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Vasculogenic Mimicry ◽  
Gastric Cancer Tissue ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Gastric Cancer Cells ◽  
Tenascin C ◽  
Gastric Cancer Patients

AbstractGastric cancer is one of the most common malignancies worldwide and vasculogenic mimicry (VM) is considered to be the leading cause for the failure of anti-angiogenesis therapy in advanced gastric cancer patients. In the present study, we investigate the role of tenascin-c (TNC) in the formation of VM in gastric cancer and found that TNC was upregulated in gastric cancer tissue than in the corresponding adjacent tissues and correlated with VM and poor prognosis of gastric cancer. Furthermore, knockdown of TNC significantly inhibited VM formation and proliferation of gastric cancer cells in vitro and in vivo, with a reduction in cell migration and invasion. Mechanistically, TNC knockdown suppressed the phosphorylation of ERK and subsequently inhibited the process of EMT, both of which play an important role in VM formation. Our results indicated that TNC plays an important role in VM formation in gastric cancer. Combining inhibition of TNC and ERK may be a potential therapeutic approach to inhibit gastric cancer growth and metastasis and decrease antiangiogenic therapeutic resistance.

BDNF expression and systemic dissemination via anoikis resistance in gastric cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14541-e14541
Author(s):  
Yoshinaga Okugawa ◽  
Yasuhiro Inoue ◽  
Koji Tanaka ◽  
Mikio Kawamura ◽  
Susumu Saigusa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Peritoneal Dissemination ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Anoikis Resistance ◽  
Bdnf Expression ◽  
Node Metastasis ◽  
Systemic Dissemination

e14541 Background: Anoikis (apoptosis resulting from loss of cell-matrix interaction) has been suggested to act as a physiological barrier to metastasis, and resistance to anoikis is necessary for cancer cell survival during systemic dissemination and metastasis. Brain-derived neurotrophic factor (BDNF) is one of the member of neurotropin family known to activate the high affinity tyrosine kinase (Trk)B receptor as a specific suppressor of anoikis. TrkB activation by BDNF has been shown to facilitate the progression of several cancers, however no reports have shown the clinical and biological effects of BDNF/TrkB axis in gastric cancer. Methods: BDNF expression in gastric cancer tissue and clinicopathological data from 153 consective patients were analyzed by real-time PCR and immunohistochemistry. The extent of target gene expression was calculated from the standard curve, with quantitative normalization of the cDNA in each sample performed using GAPDH gene as an internal control. Recombinant human BDNF and Trk antagonist K252a were used for in vitro assays to evaluate the biological role of the BDNF/TrkB axis in gastric cancer cell lines. Results: The mean BDNF level in gastric cancer tissue was 284.5 (0-2834). One hundred eighteen (77.1%) of 153 patients showed detectable BDNF levels, whereas the remainder had no detectable. BDNF positive expression was significantly associated with histological diffuse type (p=0.019), lymph node metastasis (p<0.001), peritoneal dissemination (p=0.028) and poor prognosis (p=0.022). In addition, BDNF expression is an independent risk factor for lymph node metastasis and peritoneal dissemination. Immunohistochemical analysis indicated intense BDNF expression in the cytoplasm of cancer cells, and intense TrkB expression in the nuclei of cancer cells, respectively. In vitro, administration of recombinant human BDNF promoted proliferation, anoikis resistance, and partial migration. In addition, these effects were generally inhibited by Trk antagonist K252a. Conclusions: BDNF appears to play an important role in gastric cancer progression, and blocking BDNF/TrkB axis might be clinically useful in developing therapies for patients with gastric cancer.

scholarly journals NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Yuanbo Hu ◽  
Chenbin Chen ◽  
Xinya Tong ◽  
Sian Chen ◽  
Xianjing Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Treatment Options ◽  
Biological Significance ◽  
Tissue Microarrays ◽  
Migration And Invasion ◽  
Multiple Cancer ◽  
Carcinogenic Activity

AbstractThe 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.

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