Immunohistochemical Analysis of the Expression of Adhesion Proteins: TNS1, TNS2 and TNS3 in Correlation with Clinicopathological Parameters in Gastric Cancer

Tensins belong to the group of adhesion proteins that are involved in cell adhesion and migration, actin cytoskeleton maintenance and intercellular communication. TNS1, TNS2 and TNS3 proteins expression was evaluated in 90 patients with gastric cancer by immunohistochemistry method. TNS1 was more frequently present in non-differentiated tumors compared to poorly and moderately differentiated tumors (p = 0.016). TNS1 was also more often observed in metastatic tumors compared to those without distant metastases (p = 0.001). TNS2 was more common in moderately differentiated tumors than in poorly or non-differentiated ones (p = 0.041). TNS2 expression was also more frequently present in tumors with peritumoral inflammation (p = 0.041) and with concomitant H. pylori infection (p = 0.023). In contrast, TNS3 protein was more prevalent in moderately than in poorly and non-differentiated tumors (p = 0.023). No significant relationship was found between tensins’ expression and the overall survival rate of patients. TNS1 protein expression is associated with a poor-prognosis type of GC. Higher expression of TNS2 is accompanied by peritumoral inflammation and H. pylori infection, which favor the development of GC of a better prognosis, similarly to higher TNS3 protein expression.

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Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis

Cancer Cell International ◽

10.1186/s12935-021-02077-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zeyang Wang ◽

Zhi Lv ◽

Qian Xu ◽

Liping Sun ◽

Yuan Yuan

Keyword(s):

Gastric Cancer ◽

Functional Analysis ◽

Protein Expression ◽

Epstein Barr Virus ◽

Protein Profile ◽

Expression Patterns ◽

Clinicopathological Parameters ◽

Differential Proteomics ◽

Barr Virus ◽

Epstein Barr

Abstract Background Epstein-Barr virus-associated gastric cancer (EBVaGC) is the most common EBV-related malignancy. A comprehensive research for the protein expression patterns in EBVaGC established by high-throughput assay remains lacking. In the present study, the protein profile in EBVaGC tissue was explored and related functional analysis was performed. Methods Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) was applied to EBV detection in GC cases. Data-independent acquisition (DIA) mass spectrometry (MS) was performed for proteomics assay of EBVaGC. Functional analysis of identified proteins was conducted with bioinformatics methods. Immunohistochemistry (IHC) staining was employed to detect protein expression in tissue. Results The proteomics study for EBVaGC was conducted with 7 pairs of GC cases. A total of 137 differentially expressed proteins in EBV-positive GC group were identified compared with EBV-negative GC group. A PPI network was constructed for all of them, and several proteins with relatively high interaction degrees could be the hub genes in EBVaGC. Gene enrichment analysis showed they might be involved in the biological pathways related to energy and biochemical metabolism. Combined with GEO datasets, a highly associated protein (GBP5) with EBVaGC was screened out and validated with IHC staining. Further analyses demonstrated that GBP5 protein might be associated with clinicopathological parameters and EBV infection in GC. Conclusions The newly identified proteins with significant differences and potential central roles could be applied as diagnostic markers of EBVaGC. Our study would provide research clues for EBVaGC pathogenesis as well as novel targets for the molecular-targeted therapy of EBVaGC.

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LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1922692117 ◽

2020 ◽

Vol 117 (28) ◽

pp. 16516-16526 ◽

Cited By ~ 3

Author(s):

Ting Tao ◽

Hui Shi ◽

Luca Mariani ◽

Brian J. Abraham ◽

Adam D. Durbin ◽

...

Keyword(s):

Neuroblastoma Cells ◽

Neuronal Cell ◽

Distant Metastases ◽

Malignant Cell ◽

Gene Promoters ◽

Invasion And Migration ◽

Protein Protein Interaction ◽

Cell Adhesion And Migration ◽

And Migration

LIN28B is highly expressed in neuroblastoma and promotes tumorigenesis, at least, in part, through inhibition oflet-7microRNA biogenesis. Here, we report that overexpression of either wild-type (WT) LIN28B or a LIN28B mutant that is unable to inhibitlet-7processing increases the penetrance of MYCN-induced neuroblastoma, potentiates the invasion and migration of transformed sympathetic neuroblasts, and drives distant metastases in vivo. Genome-wide chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) and coimmunoprecipitation experiments show that LIN28B binds active gene promoters in neuroblastoma cells through protein–protein interaction with the sequence-specific zinc-finger transcription factor ZNF143 and activates the expression of downstream targets, including transcription factors forming the adrenergic core regulatory circuitry that controls the malignant cell state in neuroblastoma as well asGSK3BandL1CAMthat are involved in neuronal cell adhesion and migration. These findings reveal an unexpectedlet-7–independent function of LIN28B in transcriptional regulation during neuroblastoma pathogenesis.

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Expression and Clinical Significance of ILF2 in Gastric Cancer

Disease Markers ◽

10.1155/2017/4387081 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Zi-huan Yin ◽

Xing-wang Jiang ◽

Wu-bing Shi ◽

Qian-le Gui ◽

Dong-feng Yu

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Clinical Significance ◽

Disease Free Survival ◽

High Expression ◽

Clinicopathological Parameters ◽

Rank Test ◽

Depth Of Invasion ◽

Clinical Prognosis ◽

Expression Levels

The aim of this study is to investigate the expression levels and clinical significance of ILF2 in gastric cancer. The mRNA and protein expression levels of ILF2 were, respectively, examined by quantitative real-time PCR (qRT-PCR) and Western blot from 21 paired fresh frozen GC tissues and corresponding normal gastric tissues. In order to analyze the expression pattern of ILF2 in GC, 60 paired paraffin-embedded GC slides and corresponding normal gastric slides were detected by immunohistochemistry (IHC) assay. The correlation between ILF2 protein expression levels and clinicopathological parameters, overall survival (OS), disease-free survival (DFS), and clinical prognosis were analyzed by statistical methods. Significantly higher levels of ILF2 were detected in GC tissues compared with normal controls at both mRNA and protein level. High expression of ILF2 was tightly correlated with depth of invasion, lymph node metastasis, pathological stage, and histological differentiation. Log-rank test showed that high expression of ILF2 was positively associated with poor clinical prognosis. Multivariate analysis identified that ILF2 was an independent prognostic factor for OS and DFS. Our findings suggest that ILF2 may be a valuable biomarker and a novel potential prognosis predictor for GC patients.

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Helicobacter pylori Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis

Microorganisms ◽

10.3390/microorganisms8071019 ◽

2020 ◽

Vol 8 (7) ◽

pp. 1019

Author(s):

Warner Alpízar-Alpízar ◽

Mette E. Skindersoe ◽

Lone Rasmussen ◽

Mette C. Kriegbaum ◽

Ib J. Christensen ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Epithelial Cells ◽

Protein Expression ◽

De Novo ◽

Urokinase Receptor ◽

Gastric Epithelium ◽

Upar Expression ◽

H Pylori

(1) Background: Persistent Helicobacter pylori infection is the most important risk factor for gastric cancer. The urokinase receptor (uPAR) is upregulated in lesions harboring cancer invasion and inflammation. Circumstantial evidence tends to correlate H. pylori colonization with increased uPAR expression in the human gastric epithelium, but a direct causative link has not yet been established in vivo; (2) Methods: In a mouse model of H. pylori-induced gastritis, we investigated the temporal emergence of uPAR protein expression in the gastric mucosa in response to H. pylori (SS1 strain) infection; (3) Results: We observed intense uPAR immunoreactivity in foveolar epithelial cells of the gastric corpus due to de novo synthesis, compared to non-infected animals. This uPAR induction represents a very early response, but it increases progressively over time as do infiltrating immune cells. Eradication of H. pylori infection by antimicrobial therapy causes a regression of uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by prostaglandin E2 treatment attenuates uPAR expression. Notwithstanding this relationship, H. pylori does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We showed that persistent H. pylori colonization is a necessary event for the emergence of a relatively high uPAR protein expression in murine gastric epithelial cells.

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A study on the effect of Helicobacter pylori infection on p53 expression in gastric cancer and gastritis tissues

The Journal of Infection in Developing Countries ◽

10.3855/jidc.2993 ◽

2013 ◽

Vol 7 (09) ◽

pp. 651-657 ◽

Cited By ~ 9

Author(s):

Barik A Salih ◽

Zuhal Gucin ◽

Nizamettin Bayyurt

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

P53 Protein ◽

Immunohistochemical Analysis ◽

Intestinal Type ◽

Diffuse Type ◽

P53 Expression ◽

Normal Tissues ◽

Genotype Frequencies ◽

H Pylori

Introduction: Helicobacter pylori cause damage to gastric epithelial cells and alterations in the p53 gene that lead to cancer development. This study aimed to determine the correlation of p53 expression with H. pylori using immunohistochemistry, RFLP-PCR, and histopathology. Methodology: Gastric biopsy samples from gastric cancer (GC) (n = 54) and gastritis (n = 31) patients were examined for histopathological changes and expression of p53 protein by immunohistochemistry. Results: Immunohistochemical analysis of p53 protein expression in H. pylori-positive GC sections showed an average of 44.3% positive cells in tumors and 6.9% in normal tissues, as compared to 16.4% and 4.4% in H. pylori-negative sections. P53 expression showed significant association with H. pylori (P = 0.005), invasion depth (P = 0.029) and inflammation reaction (P = 0.008). In gastritis sections, no difference in the average p53 staining in H. pylori-positive or -negative sections was seen. PCR-RFLP results also showed no difference in genotype frequencies of p53 in H. pylori-positive or -negative gastritis sections. Histopathology study of H. pylori-positive GC sections showed that 97.2% were the intestinal type and 2.8% the diffuse type, while in H. pylori-negative sections 35.2% were the intestinal type and 64.8% the diffuse type. Biopsy sections from H. pylori-positive gastritis patients revealed more severe inflammation than those of H. pylori-negative patients. Conclusion: Our results show that H. pylori infection affects p53 expression in GC. The average p53 expression was significantly higher in tumor than in normal tissues. In gastritis sections p53 expression was significantly associated with H. pylori.

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E-Cadherin and Gastric Cancer: Cause, Consequence, and Applications

BioMed Research International ◽

10.1155/2014/637308 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 40

Author(s):

Xin Liu ◽

Kent-Man Chu

Keyword(s):

Gastric Cancer ◽

Signaling Pathways ◽

Diffuse Gastric Cancer ◽

Dna Hypermethylation ◽

Invasion And Migration ◽

Transmembrane Glycoprotein ◽

Cancer Initiation ◽

And Migration ◽

H Pylori ◽

E Cadherin

E-cadherin (epithelial-cadherin), encoded by theCDH1gene, is a transmembrane glycoprotein playing a crucial role in maintaining cell-cell adhesion. E-cadherin has been reported to be a tumor suppressor and to be down regulated in gastric cancer. Besides genetic mutations inCDH1gene to induce hereditary diffuse gastric cancer (HDGC), epigenetic factors such as DNA hypermethylation also contribute to the reduction of E-cadherin in gastric carcinogenesis. In addition, expression of E-cadherin could be mediated by infectious agents such asH. pylori (Helicobacter pylori).As E-cadherin is vitally involved in signaling pathways modulating cell proliferation, survival, invasion, and migration, dysregulation of E-cadherin leads to dysfunction of gastric epithelial cells and contributes to gastric cancer development. Moreover, changes in its expression could reflect pathological conditions of gastric mucosa, making its role in gastric cancer complicated. In this review, we summarize the functions of E-cadherin and the signaling pathways it regulates. We aim to provide comprehensive perspectives in the molecular mechanism of E-cadherin and its involvement in gastric cancer initiation and progression. We also focus on its applications for early diagnosis, prognosis, and therapy in gastric cancer in order to open new avenues in this field.

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Prognostic value of noggin protein expression in patients with resected gastric cancer

BMC Cancer ◽

10.1186/s12885-021-08273-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sang Hoon Chun ◽

Eun Young Kim ◽

Jung-Sook Yoon ◽

Hye Sung Won ◽

Kwangil Yim ◽

...

Keyword(s):

Gastric Cancer ◽

Prognostic Factor ◽

Protein Expression ◽

Rna Binding ◽

Lymphatic Invasion ◽

Intestinal Type ◽

Clinicopathological Parameters ◽

Invasive Front ◽

Tumor Center ◽

Resected Gastric Cancer

Abstract Background Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. Methods A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. Results RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P < 0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P < 0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35–0.97, P < 0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81–2.26, P = 0.251). Conclusions Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.

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Helicobacter pylori-Induced Heparanase Promotes H. pylori Colonization and Gastritis

Frontiers in Immunology ◽

10.3389/fimmu.2021.675747 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li Tang ◽

Bo Tang ◽

Yuanyuan Lei ◽

Min Yang ◽

Sumin Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Heparan Sulfate ◽

Chronic Gastritis ◽

Immune Cells ◽

Mapk Signaling ◽

Inflammatory Conditions ◽

Cytokines And Chemokines ◽

And Migration ◽

H Pylori

Chronic gastritis caused by Helicobacter pylori (H. pylori) infection has been widely recognized as the most important risk factor for gastric cancer. Analysis of the interaction between the key participants in gastric mucosal immunity and H. pylori infection is expected to provide important insights for the treatment of chronic gastritis and the prevention of gastric cancer. Heparanase is an endoglycosidase that degrades heparan sulfate, resulting in remodeling of the extracellular matrix thereby facilitating the extravasation and migration of immune cells towards sites of inflammation. Heparanase also releases heparan sulfate-bound cytokines and chemokines that further promote directed motility and recruitment of immune cells. Heparanase is highly expressed in a variety of inflammatory conditions and diseases, but its role in chronic gastritis has not been sufficiently explored. In this study, we report that H. pylori infection promotes up-regulation of heparanase in gastritis, which in turn facilitates the colonization of H. pylori in the gastric mucosa, thereby aggravating gastritis. By sustaining continuous activation, polarization and recruitment of macrophages that supply pro-inflammatory and pro-tumorigenic cytokines (i.e., IL-1, IL-6, IL-1β, TNF-α, MIP-2, iNOS), heparanase participates in the generation of a vicious circle, driven by enhanced NFκB and p38-MAPK signaling, that supports the development and progression of gastric cancer. These results suggest that inhibition of heparanase may block this self-sustaining cycle, and thereby reduce the risk of gastritis and gastric cancer.

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Implication of expression of MMR proteins and clinicopathological characteristics in gastric cancer

Asia-Pacific Journal of Oncology ◽

10.32948/ajo.2020.12.30 ◽

2020 ◽

pp. 1-7

Author(s):

Renu Verma ◽

Puja Sakhuja ◽

Ritu Srivastava ◽

Prakash Chand Sharma

Keyword(s):

Gastric Cancer ◽

Protein Expression ◽

Mismatch Repair ◽

Univariate Analysis ◽

Immunohistochemical Analysis ◽

Tumor Location ◽

Clinicopathological Characteristics ◽

Depth Of Invasion ◽

Mismatch Repair Proteins ◽

Mmr Proteins

Introduction Microsatellite instability (MSI), referred to as variations at microsatellite loci, at mismatch repair (MMR) genes leads to the formation of an aberrant MMR system that fails to rectify errors occurring during DNA replication. MMR deficiency can be assessed by immunohistochemical analysis of the expression of mismatch repair proteins in the target tissues. Methods We investigated the expression of four key MMR proteins (MLH1, MSH2, MSH6, and PMS2) in formalin-fixed paraffin-embedded (FFPE) tumor and normal tissues obtained from thirty gastric cancer (GC) patients. The association of clinicopathological features with MMR status was also analyzed. Results A total of 12 (40%) GC patients exhibited loss of expression of MMR proteins, including loss of MLH1 and PMS2 in 3 cases and loss of MSH2 and MSH6 in 4 cases. Univariate analysis showed an association of loss of MMR protein expression with moderately differentiated GC. However, there was no statistically significant association between loss of MMR protein expression with gender, tumor location, depth of invasion, lymph node metastasis, WHO classification, lympho-vascular invasion, and infection with H. pylori. Conclusion Our results implicate the role of mismatch repair proteins in gastric tumorigenesis. The MMR protein status is an important aspect of tumorigenesis and can be prescribed for the screening of GC.

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