TRPV2 Calcium Channel Gene Expression and Outcomes in Gastric Cancer Patients: A Clinically Relevant Association

Gastric cancer (GC) is characterized by poor efficacy and the modest clinical impact of current therapies. Apoptosis evasion represents a causative factor for treatment failure in GC as in other cancers. Since intracellular calcium homeostasis regulation has been found to be associated with apoptosis resistance, the aberrant expression of intracellular calcium regulator genes (CaRGs) could have a prognostic value in GC patients. We analyzed the association of the expression levels of 98 CaRGs with prognosis by the log-rank test in a collection of 1524 GC samples from four gene expression profiling datasets. We also evaluated differential gene expression in comparison with normal stomach tissue, and then we crossed results with tissue microarrays from the Human Protein Atlas. Among the investigated CaRGs, patients with high levels of TRPV2 expression were characterized by a shorter overall survival. TRPV2 expression was found to increase according to tumor stage. Both mRNA and protein levels were significantly higher in tumor than normal stomach samples. TRPV2 was also associated with poor prognosis in the Lauren’s intestinal type GC and in patients treated with adjuvant therapy. Overall, we highlighted the relevance of TRPV2 not only as a prognostic biomarker but also as a potential therapeutic target to improve GC treatment efficacy.

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Determination of Affected Factor on Survival Rates In Referral Gastric Cancer Patients to Imam Khomeini Clinic in Hamadan Province from 2004-2017

Journal of Shahid Sadoughi University of Medical Sciences ◽

10.18502/ssu.v27i12.2832 ◽

2020 ◽

Author(s):

Fatemeh Gohari-Ensaf ◽

Zeinab Berangi ◽

Mohamad Abbasi ◽

Ghodratollah Roshanaei

Keyword(s):

Gastric Cancer ◽

Survival Rate ◽

Screening Program ◽

Survival Rates ◽

Tumor Stage ◽

Rank Test ◽

Significance Level ◽

Kaplan Meier ◽

One Year ◽

Gastric Cancer Patients

Introduction: Gastric cancer is the fourth most common cancer and the second leading cause of death in the world. Despite the recent advances in controlling and treating the disease, the survival rate of this cancer is relatively low. Various factors can affect the survival of the patients with gastric cancer. The aim of this study was to determine the survival rates and the effective factors in the patients with gastric cancer. Methods: The study population included all the patients diagnosed with gastric cancer in Hamadan Province who were referred to Hamadan Imam Khomeini Specialized Clinic between 2004 to 2017. Patients were followed up by periodical referrals and/or telephone contact. The survival rate of the patients was calculated using Kaplan-Meier method and effective survival factors with Cox proportional regression. Data were analyzed using SPSS 23 software at a significance level of 0.05. Results: Out of the 350 patients with gastric cancer, 74.3% were male and 25.7% were female. One-year, three-year and five-year survival rates were 67%, 36% and 27%, respectively. The log -rank test showed that age, type of tumor, stage of disease, type of Surgery and metastasis of the disease were effective on the survival of patients. In Cox's multivariate analysis, the only age variables at the time of diagnosis and chemotherapy were survival variables. (P<0.05). Conclusion: The results of this study showed that age variable is a strong factor in survival, so it is essential to diagnose the disease at the early age and early stages of the disease using a screening program.

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Circular RNA hsa_circ_000780 has been identified by genomic expression profile analysis as a potential diagnostic marker for gastric cancer

10.21203/rs.3.rs-20318/v2 ◽

2020 ◽

Author(s):

Jian Song ◽

Shuyong Yu ◽

Dunjing Zhong ◽

Weizhong Yang ◽

Zhen Jia ◽

...

Keyword(s):

Gastric Cancer ◽

Expression Profile ◽

Profile Analysis ◽

Quantitative Polymerase Chain Reaction ◽

Venous Invasion ◽

Tumor Stage ◽

Circular Rna ◽

Chronic Atrophic Gastritis ◽

Gastric Fluid ◽

Aberrant Expression

Abstract Background : The present study attempted to detect a specific circular RNA (circRNA) for the early diagnosis of gastric cancer (GC). Methods: We selected four patients with GC for this study. The total RNA of the malignant and adjacent tissues was extracted, and the circRNA was screened. The eight most upregulated and downregulated circRNAs with a statistically significant relation to GC and paired adjacent nontumorous tissues were identified using real-time fluorescent quantitative polymerase chain reaction (PCR). CircRNA expression was identified by quantitative reverse transcriptase PCR in 78 cases of GC and adjacent tissues, and in the gastric fluids of 30 patients with chronic nonatrophic gastritis, 30 patients with chronic atrophic gastritis, 21 with early GC, and 57 with advanced GC. Results: A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significant aberrant expression in GC tissues. A majority of the differentially expressed circRNAs originated from chr1, chr3, chr4, chr6, and chr11. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissues, and its level in GC tissues correlated with the tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen, and carbohydrate antigen 19-9 expression. A crucial observation was the presence of this circRNA in the gastric fluid of patients with early and advanced GC. Conclusions: The present study uncovered a new hsa_circRNA expression profile in human GC, of which hsa_circ_000780 was significantly downregulated in GC tissues and in gastric fluid. It can be potentially used as a novel biomarker for early GC screening.

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Identification of prognostic biomarkers for gastric cancer by gene expression analysis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4623 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4623-4623

Author(s):

Y. Yamada ◽

T. Arao ◽

K. Nishio ◽

F. Koizumi ◽

D. Saito ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Overall Survival ◽

Real Time ◽

Prognostic Biomarkers ◽

Rank Test ◽

Pcr Analysis ◽

Rt Pcr ◽

Test Set ◽

Validation Set

4623 Background: Endoscopic biopsy before chemotherapy provides an excellent opportunity for studying biomarkers related to therapy-induced tumor responses or overall survival. This study was designed to identify prognostic biomarkers in patients with unresected gastric cancer. Methods: Samples were taken from histologically proved primary gastric cancers in 40 patients before chemotherapy. Microarray analysis was performed using Affymetrix HG-U133Plus2.0 GeneChips after RNA quality checks of the samples. Correlations between gene expression data and survival time were statistically evaluated with a univariate Cox proportional-hazards model. Identified genes were validated by real time RT-PCR analysis in same 40 test-set samples. Then, PCR-validated genes were evaluated for independent samples (validation set) to predict survival. Results: We obtained 185 candidate genes that were significantly associated with survival (p<0.005) on univariate testing in the 40 test-set sample. Real time RT-PCR analysis identified 5 genes that were reproducibly related to survival on the log-rank test (p<0.01). PCR analysis with each of these 5 genes discriminated short-term survivors with a sensitivity of 71% and a specificity of 46–77% in the test set. For the independent 19-sample validation set, single-gene PCR analysis had a sensitivity of 50–81% and a specificity of 38–62%. A multi-gene prediction panel will be evaluated. Conclusions: Gene expression profiling by microarray and real time RT-PCR is useful for predicting overall survival in gastric cancer. No significant financial relationships to disclose.

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RNA-Binding Proteins in Pulmonary Hypertension

International Journal of Molecular Sciences ◽

10.3390/ijms21113757 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3757 ◽

Cited By ~ 1

Author(s):

Hui Zhang ◽

R. Dale Brown ◽

Kurt R. Stenmark ◽

Cheng-Jun Hu

Keyword(s):

Gene Expression ◽

Pulmonary Hypertension ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Current Knowledge ◽

Critical Role ◽

Apoptosis Resistance ◽

Aberrant Expression ◽

Expression Of Genes

Pulmonary hypertension (PH) is a life-threatening disease characterized by significant vascular remodeling and aberrant expression of genes involved in inflammation, apoptosis resistance, proliferation, and metabolism. Effective therapeutic strategies are limited, as mechanisms underlying PH pathophysiology, especially abnormal expression of genes, remain unclear. Most PH studies on gene expression have focused on gene transcription. However, post-transcriptional alterations have been shown to play a critical role in inflammation and metabolic changes in diseases such as cancer and systemic cardiovascular diseases. In these diseases, RNA-binding proteins (RBPs) have been recognized as important regulators of aberrant gene expression via post-transcriptional regulation; however, their role in PH is less clear. Identifying RBPs in PH is of great importance to better understand PH pathophysiology and to identify new targets for PH treatment. In this manuscript, we review the current knowledge on the role of dysregulated RBPs in abnormal mRNA gene expression as well as aberrant non-coding RNA processing and expression (e.g., miRNAs) in PH.

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The Variant rs145204276 of GAS5 is Associated with the Development and Prognosis of Gastric Cancer

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.271.qjl ◽

2018 ◽

Vol 27 (1) ◽

pp. 19-24 ◽

Cited By ~ 7

Author(s):

Qianjun Li ◽

Gang Ma ◽

Huimin Guo ◽

Suhua Sun ◽

Ying Xu ◽

...

Keyword(s):

Gastric Cancer ◽

Survival Rate ◽

Cancer Progression ◽

Regulatory Mechanism ◽

Tumor Stage ◽

Kaplan Meier ◽

Non Coding Rna ◽

Early Tumor ◽

Long Non Coding Rna ◽

Clinicopathological Variables

Background & Aims: Down-regulation of the growth arrest specific transcript 5 (GAS5) (long non-coding RNA) is associated with cell proliferation of gastric cancer (GC) and a poor prognosis. We aimed to investigate whether the variant rs145204276 of GAS5 is associated with the prognosis of GC in the Chinese population, and to unveil the regulatory mechanism underlying the GAS5 expression in GC tissues.Method: 1,253 GC patients and 1,354 healthy controls were included. The frequency of the genotype del/del and the allele del of rs145204276 were compared between the patients and the controls and between different subgroups of patients classified by clinicopathological variables. The overall survival rate was analyzed according to the Kaplan-Meier method using the log-rank test.Results: The frequency of genotype del/del was significantly lower in patients than in the controls (7.0% vs. 9.1%, p = 0.001). Kaplan-Meier analysis showed that genotype del/del was significantly associated with a higher survival rate (p = 0.01). Patients with late tumor stage were found to have a significantly lower rate of genotype del/del than those with an early tumor stage (4.9% vs. 8.8%, p = 0.01). Patients with UICC III and IV were found to have a significantly lower rate of genotype del/del than those with UICC I and II (5.3% vs. 8.1%, p = 0.02).Conclusion: The variant rs145204276 of GAS5 is associated with the development and prognosis of GC. The allele del of rs145204276 is associated with a remarkably lower incidence of cancer progression and metastasis.

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Effects of Chinese herbal recipe Weichang'an in inducing apoptosis and related gene expression in human gastric cancer grafted onto nude mice

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20070312 ◽

2007 ◽

Vol 5 (3) ◽

pp. 287-297 ◽

Cited By ~ 2

Author(s):

Aiguang Zhao

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Nude Mice ◽

Human Gastric Cancer ◽

Related Gene ◽

Chinese Herbal

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Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2007935117 ◽

2020 ◽

Vol 117 (48) ◽

pp. 30639-30648

Author(s):

Dan Hu ◽

Emily C. Tjon ◽

Karin M. Andersson ◽

Gabriela M. Molica ◽

Minh C. Pham ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

T Cells ◽

Transcription Factor ◽

Proinflammatory Cytokines ◽

Th17 Cells ◽

Gene Set Enrichment Analysis ◽

Aberrant Expression ◽

Signature Genes ◽

The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

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A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

Genes ◽

10.3390/genes12060854 ◽

2021 ◽

Vol 12 (6) ◽

pp. 854

Author(s):

Yishu Wang ◽

Lingyun Xu ◽

Dongmei Ai

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Dna Methylation ◽

Regression Model ◽

The Cancer Genome Atlas ◽

Low Rank ◽

Expression Levels ◽

Rank Regression ◽

Prediction Of Prognosis ◽

Gene Expression Levels

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

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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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