scholarly journals The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 394 ◽  
Author(s):  
Ana Margarida Moreira ◽  
Joana Pereira ◽  
Soraia Melo ◽  
Maria Sofia Fernandes ◽  
Patrícia Carneiro ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Extracellular Matrix ◽  
Expression Patterns ◽  
Predictive Biomarkers ◽  
Gastric Epithelium ◽  
Comprehensive Overview ◽  
Diagnostic Biomarkers ◽  
Malignant Lesions ◽  
And Behavior ◽  
Disease Stages

The extracellular matrix (ECM) is a dynamic and highly organized tissue structure, providing support and maintaining normal epithelial architecture. In the last decade, increasing evidence has emerged demonstrating that alterations in ECM composition and assembly strongly affect cellular function and behavior. Even though the detailed mechanisms underlying cell-ECM crosstalk are yet to unravel, it is well established that ECM deregulation accompanies the development of many pathological conditions, such as gastric cancer. Notably, gastric cancer remains a worldwide concern, representing the third most frequent cause of cancer-associated deaths. Despite increased surveillance protocols, patients are usually diagnosed at advanced disease stages, urging the identification of novel diagnostic biomarkers and efficient therapeutic strategies. In this review, we provide a comprehensive overview regarding expression patterns of ECM components and cognate receptors described in normal gastric epithelium, pre-malignant lesions, and gastric carcinomas. Important insights are also discussed for the use of ECM-associated molecules as predictive biomarkers of the disease or as potential targets in gastric cancer.

scholarly journals Evaluation of Important Molecular Pathways and Candidate Diagnostic Biomarkers of Noninvasive to Invasive Stages in Gastric Cancer by In Silico Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sara Tutunchi ◽  
Saeedeh Akhavan ◽  
Ahmad Bereimipour ◽  
Sayyed Mohammad Hossein Ghaderian
Keyword(s):  
Gastric Cancer ◽  
Extracellular Matrix ◽  
Bioinformatics Analysis ◽  
In Silico Analysis ◽  
Protein Network ◽  
Diagnostic Biomarkers ◽  
Highly Expressed Genes ◽  
Diagnosis Of Cancer ◽  
Speed Up ◽  
Gastric Cancer Patients

Gastric cancer affects millions of people each year; it is the fifth deadliest cancer globally. Due to failure to perform routine tests such as endoscopy, it is usually diagnosed in the invasive stages. Therefore, finding diagnostic biomarkers in blood can help to speed up the initial diagnosis of cancer. This study aimed to find appropriate diagnostic biomarkers in the extracellular matrix of noninvasive to invasive stages of gastric cancer patients, using bioinformatics analysis. First, we selected the appropriate datasets from the GEO database. We evaluated the genes’ signaling pathways, biological processes, and molecular functions. More accurately, we assessed the genes, in which their protein products are released into the extracellular matrix; we evaluated their protein network. Then, we validated the candidate proteins in the GEPIA and TCGA databases. The extracellular matrix, tyrosine kinase receptors, and immune response pathways are effective factors, which are related to the highly expressed genes and metabolism; cell cycle pathways are also impressive on low-expression genes. 69 highly expressed proteins are released into the extracellular matrix. After drawing the protein network, 5 proteins were selected as more suitable candidates for further studies. These proteins’ expression significantly increases in the human samples, and the survival chart showed up to about 80% mortality in the individuals over time. With integrated bioinformatics analysis, BGN, LOX, MMP-9, SERPINE1, and TGFB1 proteins have been selected as suitable diagnostic biomarkers for noninvasive to invasive stages of gastric cancer. Further studies are needed to evaluate more precise mechanisms between these proteins.

scholarly journals Comprehensive Analysis of IGFBPs as Biomarkers in Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Liu ◽  
Jianwu Jiang ◽  
Xiefu Zhang ◽  
Meixiang Zhang ◽  
Yang Fu
Keyword(s):  
Gastric Cancer ◽  
Extracellular Matrix ◽  
Overall Survival ◽  
Prognostic Value ◽  
Expression Patterns ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Comprehensive Analysis ◽  
Free Survival ◽  
Disease Free

ObjectiveGastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. Insulin-like growth-factor-binding proteins (IGFBPs) were initially identified as passive inhibitors that combined with insulin-like growth factors (IGFs) in serum. However, more recent data have shown that they have different expression patterns and a variety of functions in the development and occurrence of cancers. Thus, their various roles in cancer still need to be elucidated. This study aimed to explore the IGFBPs and their prognostic value as markers in gastric cancer.MethodsOncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier Plotter, cBioPortal, GeneMANIA, and TIMER were used to analyze the differential expression, prognostic value, genetic alteration, and association with immune cell infiltration of IGFPBs in gastric cancer.ResultsExpression levels of IGFBP3, IGFBP4, and IGFBP7 were significantly elevated in gastric cancer tissues, whereas those of IGFBP1 were reduced in normal tissues. IGFBP1/5/7 expression was significantly associated with overall survival whereas IGFBP6/7 expression was significantly correlated with disease-free survival in gastric cancer patients. IGFBP3/5/6/7 were associated with clinical cancer stage. Gene ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that IGFBP3/5/7 were mainly enriched in focal adhesion, extracellular matrix structural constituent, cell-substratist junction, extracellular structure, and matrix organization. Stomach adenocarcinoma (STAD) and gastric cancer had more IGFBP1–7 mutations than other tumor types. Hub gene analysis showed that TP53 and IGF2 expression was significantly elevated in STAD patients; PLG, PAPPA, AFP, and CYR61 were associated with overall survival rate; and IGFALS, PLG, IGF1, AHSG, and FN1 were associated with disease-free survival. Finally, IGFBP3–7 were all associated with cancer-associated fibroblast infiltration in STAD, colon adenocarcinoma, and rectal adenocarcinoma.ConclusionOur study provides a comprehensive analysis and selection of IGFBPs as prognostic biomarkers in STAD. This was the first bioinformatic analysis study to describe the involvement of IGFBPs, especially IGFBP7, in gastric cancer development through the extracellular matrix.

scholarly journals Long Non-Coding RNAs in Gliomas: From Molecular Pathology to Diagnostic Biomarkers and Therapeutic Targets

2018 ◽  
Vol 19 (9) ◽  
pp. 2754 ◽  
Author(s):  
Marek Vecera ◽  
Jiri Sana ◽  
Radim Lipina ◽  
Martin Smrcka ◽  
Ondrej Slaby
Keyword(s):  
Molecular Pathology ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Biological Behavior ◽  
Diagnostic Biomarkers ◽  
Non Coding Rnas

Gliomas are the most common malignancies of the central nervous system. Because of tumor localization and the biological behavior of tumor cells, gliomas are characterized by very poor prognosis. Despite significant efforts that have gone into glioma research in recent years, the therapeutic efficacy of available treatment options is still limited, and only a few clinically usable diagnostic biomarkers are available. More and more studies suggest non-coding RNAs to be promising diagnostic biomarkers and therapeutic targets in many cancers, including gliomas. One of the largest groups of these molecules is long non-coding RNAs (lncRNAs). LncRNAs show promising potential because of their unique tissue expression patterns and regulatory functions in cancer cells. Understanding the role of lncRNAs in gliomas may lead to discovery of the novel molecular mechanisms behind glioma biological features. It may also enable development of new solutions to overcome the greatest obstacles in therapy of glioma patients. In this review, we summarize the current knowledge about lncRNAs and their involvement in the molecular pathology of gliomas. A conclusion follows that these RNAs show great potential to serve as powerful diagnostic, prognostic, and predictive biomarkers as well as therapeutic targets.

Ultrastructural Cytochemical Study of Human Gastric Cancer: Observation of AKP ase,ACP ase,G6P ase,TPP ase and CO ase

1990 ◽  
Vol 48 (3) ◽  
pp. 254-255
Author(s):  
Dong Yuming ◽  
Yang Guanglin ◽  
Du Wei Dong ◽  
Xu Ai Liam
Keyword(s):  
Gastric Cancer ◽  
Gastric Epithelium ◽  
Human Gastric Cancer ◽  
Electron Microscopic ◽  
Cytochemical Study ◽  
Electron Microscopic Cytochemistry ◽  
Cytochemical Reaction ◽  
Set Up ◽  
Cancer Tissues ◽  
Cytochemical Technique

The activities and distributions of AKPase ,ACPase,G6Pase,TPPase and COase in human normal gastric mucosa and gastric cancer tissues were studied histochemically at light microscopic level. These enzymes are the marker enzymes of cell membrane lysosome endoplasmic reticulum, Golgi apparatus and mitochondrion objectively. On the basis of the research we set up a special ultrastructural cytochemical technique and first researched into gastric cancer domesticly. Ultrastructural cytochemistry is also called electron microscopic cytochemistry. This new technique possesses both the sensitivity of cytochemical reaction andi the high resolution of electron microscope. It is characterized by direct observation,exact localization and the combination morphology with function.The distributions of AKPase,ACPase,G6Pase,TPPase and COase in 14 cases of gastric cancer and 1 case of gastric Denign lesion were studied ultrastructurally. The results showed: 1. normal gastric epithelium had no AKPase reaction. The reaction of ACPase,G6Pase,TPPase and Coase were found in the corresponding organella, which were consistent with their function.

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

Identification of biomarkers and functional modules from genomic data in stage-wise breast cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Athira K ◽  
Vrinda C ◽  
Sunil Kumar P V ◽  
Gopakumar G
Keyword(s):  
Breast Cancer ◽  
Expression Patterns ◽  
Differential Expression Analysis ◽  
Predictive Biomarkers ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Functional Modules ◽  
Incidence And Mortality ◽  
Multiple Stages

Background: Breast cancer is the most common cancer in women across the world, with high incidence and mortality rates. Being a heterogeneous disease, gene expression profiling based analysis plays a significant role in understanding breast cancer. Since expression patterns of patients belonging to the same stage of breast cancer vary considerably, an integrated stage-wise analysis involving multiple samples is expected to give more comprehensive results and understanding of breast cancer. Objective: The objective of this study is to detect functionally significant modules from gene co-expression network of cancerous tissues and to extract prognostic genes related to multiple stages of breast cancer. Methods: To achieve this, a multiplex framework is modelled to map the multiple stages of breast cancer, which is followed by a modularity optimization method to identify functional modules from it. These functional modules are found to enrich many Gene Ontology terms significantly that are associated with cancer. Result and Discussion: predictive biomarkers are identified based on differential expression analysis of multiple stages of breast cancer. Conclusion: Our analysis identified 13 stage-I specific genes, 12 stage-II specific genes, and 42 stage-III specific genes that are significantly regulated and could be promising targets of breast cancer therapy. That apart, we could identify 29, 18 and 26 lncRNAs specific to stage I, stage II and stage III respectively.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

2021 ◽  
Vol 10 (7) ◽  
pp. 1412
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Andrea Botticelli ◽  
Dario Trapani ◽  
Alessandro Parisi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Implementation ◽  
T Cell Therapy ◽  
Dismal Prognosis

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.

scholarly journals Liquid Biopsy in Hepatocellular Carcinoma: Where Are We Now?

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2274
Author(s):  
Filippo Pelizzaro ◽  
Romilda Cardin ◽  
Barbara Penzo ◽  
Elisa Pinto ◽  
Alessandro Vitale ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Predictive Biomarkers ◽  
Invasive Procedure ◽  
Therapeutic Monitoring ◽  
Comprehensive Overview ◽  
Improve Patient Survival ◽  
Prognostic Tests ◽  
Prognostic Stratification ◽  
New Biomarkers

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Diagnostic, prognostic, and predictive biomarkers are urgently needed in order to improve patient survival. Indeed, the most widely used biomarkers, such as alpha-fetoprotein (AFP), have limited accuracy as both diagnostic and prognostic tests. Liver biopsy provides an insight on the biology of the tumor, but it is an invasive procedure, not routinely used, and not representative of the whole neoplasia due to the demonstrated intra-tumoral heterogeneity. In recent years, liquid biopsy, defined as the molecular analysis of cancer by-products, released by the tumor in the bloodstream, emerged as an appealing source of new biomarkers. Several studies focused on evaluating extracellular vesicles, circulating tumor cells, cell-free DNA and non-coding RNA as novel reliable biomarkers. In this review, we aimed to provide a comprehensive overview on the most relevant available evidence on novel circulating biomarkers for early diagnosis, prognostic stratification, and therapeutic monitoring. Liquid biopsy seems to be a very promising instrument and, in the near future, some of these new non-invasive tools will probably change the clinical management of HCC patients.

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

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.

Sign in / Sign up

Export Citation Format

Share Document