scholarly journals Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Mingming Wang ◽  
Changzheng Li ◽  
Ying Liu ◽  
Zuomin Wang
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Immune Cell ◽  
Expression Patterns ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Basement Membranes ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction

Background. Laminin alpha 4 (LAMA4) is widely distributed in the basement membranes of various tissues. It can regulate cancer cell proliferation and migration. We investigated the effects of LAMA4 in gastric cancer (GC). Methods. LAMA4 expression patterns were analyzed in GC using the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and UALCAN. Correlations between LAMA4 expression and clinicopathological characteristics were evaluated using data from The Cancer Genome Atlas (TCGA). The survival analysis was examined using the Kaplan-Meier plotter and GEPIA and ascertained by multivariate Cox analysis. Genetic alterations and DNA methylation of LAMA4 were analyzed using cBioPortal and MethSurv. LinkedOmics was applied to identify coexpressed genes of LAMA4. The association between LAMA4 and infiltration of immune cells was explored using Tumor Immune Estimation Resource (TIMER) and GEPIA. Results. LAMA4 was highly expressed in GC, and its upregulation significantly correlated with T classification ( P = 0.040 ). LAMA4 expression was an independent risk factor for overall survival (OS, P = 0.033 ). Patients with genetic alterations of LAMA4 showed a significantly better disease-free survival (DFS, P = 0.022 ). Ten CpG sites of LAMA4 were significantly associated with prognosis in GC. The functions of LAMA4 and coexpression genes were mainly involved in extracellular matrix (ECM) receptor interaction. LAMA4 expression significantly correlated with infiltration of macrophages ( P < 0.001 ), CD4+ T cells ( P < 0.001 ), and dendritic cells ( P < 0.001 ). Furthermore, LAMA4 expression was significantly associated with markers of M2 and tumor-associated macrophages (TAMs). Conclusion. LAMA4 expression was linked to GC prognosis and immune cell infiltration, indicating its potential use as a prognostic biomarker and therapeutic target.

scholarly journals Evaluation of the prognostic value of CBXs in gastric cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengya He ◽  
Limin Yue ◽  
Haiyan Wang ◽  
Feiyan Yu ◽  
Mingyang Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Genetic Mutation ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Interactive Analysis ◽  
Gastric Cancer Patients

AbstractChromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.

scholarly journals Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis

2017 ◽  
Vol 43 (3) ◽  
pp. 1090-1099 ◽  
Author(s):  
Zhonghua Jiang ◽  
Tingting Yu ◽  
Zhining Fan ◽  
Hongmei Yang ◽  
Xin Lin
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Strong Negative Correlation ◽  
Functional Studies ◽  
Expression Of Genes ◽  
Cancer Genome Atlas

Background/Aims: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. Methods: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. Results: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. Conclusion: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.

scholarly journals DNA methylation signatures associated with prognosis of gastric cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin Dai ◽  
Akihiro Nishi ◽  
Zhe-Xuan Li ◽  
Yang Zhang ◽  
Tong Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Risk Score ◽  
Host Gene ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Host Gene Expression ◽  
Clinical Practices ◽  
Free Interval

Abstract Background Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study. Methods Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n = 381), disease-specific survival (DSS, n = 372), and progression-free interval (PFI, n = 383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n = 247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression. Results We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed. Conclusions We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.

scholarly journals ADAM12 as a Clinical Prognostic Indicator Associated with Tumour Immune Infiltration in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Junfan Pan ◽  
Zhidong Huang ◽  
Yiquan Xu
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Model ◽  
Immune Cell ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Receptor Interaction ◽  
Significant Differential Expression ◽  
Immune Related Genes

Abstract Background: Lung cancer is the most common cause of cancer-related death worldwide. In humans, 22 functional α-disintegrinand metalloproteinases (ADAMs) have been identified, 12 of which have proteolytic activity. The role of ADAMs in cancer has attracted increasing attention. However, the expression and significance of ADAMs in lung adenocarcinoma (LUAD) remain unclear. The current study aimed to explore the expression and prognostic value of ADAM12 in LUAD.Methods: The Cancer Genome Atlas(TCGA) database was used to analyse the expression of ADAMs in LUAD. The cBioPortal database was used to obtain and analyse ADAM12 copy number changes, and the LinkedOmics database was utilised for the analysis of ADAM12-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was then performed using TIMER. The relationship between ADAM12 and the tumour immune microenvironment(TIM) was assessed via the TISIDB database. ADAM12 and immune-related genes were used to construct a prognostic model. Knockdown of ADAM12 was performed in vitro in order to verify its biological function. The unpaired t-test was used for comparison between the two groups, ANOVA was used for analysing differences between multiple groups, and the Kaplan-Meier test was used to compare survival between groups.Results: Most ADAMs exhibited significant differential expression in LUAD. ADAM12 expression was significantly higher in LUAD tissues than in healthy tissues, and lower ADAM12 expression was associated with better survival. Genetic alterations of ADAM12 mainly included missense mutations, amplifications, and deep deletions. ADAM12 and positively correlated genes were mainly enriched in protein digestion and absorption, ECM-receptor interaction, and adhesion plaques. ADAM12 had a moderate correlation with immune cell markers EBIP1, CCNB1, EXO1, KNTC1, PRC1 and FAM198B. Prognostic model was established based on ADAM12 and immune-related genes. In vitro experiments revealed that knocking down ADAM12 inhibited cell proliferation, migration and invasion.Conclusion: ADAM12 potentially plays an important role in the occurrence of LUAD and may be utilised as an immunotherapy target and a valuable prognostic biomarker for LUAD.

scholarly journals Characteristics of the Immune Cell Infiltration Landscape in Gastric Cancer to Assistant Immunotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Chenlu Li ◽  
Jingjing Pan ◽  
Yinyan Jiang ◽  
Yan Yu ◽  
Zhenlin Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Therapeutic Responses

Background: Gastric cancer (GC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable indices especially immunotherapy-associated parameters that can predict the therapeutic responses to immunotherapy of GC patients.Methods: Gene expression profile of 854 GC patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE84433) with their corresponding clinical and somatic mutation data. Based on immune cell infiltration (ICI) levels, molecular clustering classification was performed to identify subtypes and ICI scores in GC patients. After functional enrichment analysis of subtypes, we further explored the correlation between ICI scores and Tumor Mutation Burden (TMB) and the significance in clinical immunotherapy response.Results: Three subtypes were identified based on ICI scores with distinct immunological and prognostic characteristics. The ICI-cluster C, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration and up-regulation of PD-L1. ICI scores were identified through using principal component analysis (PCA) and the low ICI scores were consistent with the increased TMB and the immune-activating signaling pathways. Contrarily, the high-ICI score cluster was involved in the immunosuppressive pathways, such as TGF-beta, MAPK and WNT signaling pathways, which might be responsible for poor prognosis of GC. External immunotherapy and chemotherapy cohorts validated the patients with lower ICI scores exhibited significant therapeutic responses and clinical benefits.Conclusion: This study elucidated that ICI score could sever as an effective prognostic and predictive indicator for immunotherapy in GC. These findings indicated that the systematic assessment of tumor ICI landscapes and identification of ICI scores have crucial clinical implications and facilitate tailoring optimal immunotherapeutic strategies.

scholarly journals DNA Methylation Signatures Associated With Prognosis of Gastric Cancer

2021 ◽  
Author(s):  
Jin Dai ◽  
Akihiro Nishi ◽  
Zhe-Xuan Li ◽  
Yang Zhang ◽  
Tong Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Risk Score ◽  
Host Gene ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Host Gene Expression ◽  
Clinical Practices ◽  
Free Interval

Abstract Background: Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study.Methods: Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n=381), disease-specific survival (DSS, n=372), and progression-free interval (PFI, n=383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n=247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression.Results: We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed. Conclusions: We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.

scholarly journals Prognostic Value and Immune Characteristics of RUNX Family in Human Cancers: A Pan-cancer Analysis

2021 ◽  
Author(s):  
Han Zhao ◽  
Yun Chen ◽  
Peijun Shen ◽  
Lan Gong
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Immune Cell ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Genetic Mutation ◽  
The Cancer Genome Atlas ◽  
Different Types ◽  
Cancer Types ◽  
Pan Cancer

Abstract Background: Runt‑related transcription factors (RUNX) are involved in numerous fundamental biological processes and play crucial parts in tumorigenesis and metastasis both directly and indirectly. However, the pan-cancer evidence of RUNX gene family is no available. Methods: In this study, we analyzed the potential association between RUNX gene family expression and patient’s prognosis, immune cell infiltration, drug response, and genetic mutation data across different types of tumors using based on The Cancer Genome Atlas, Gene Expression Omnibus, and Oncomine database. Results: The results showed that the expression of the RUNX family varied among different cancer types, revealing its heterogeneity in cancers, and that expression of RUNX2 was lower than that of RUNX1 and RUNX3 across all cancer types. RUNX family gene expression was related to prognosis in several cancers. Furthermore, our study revealed a clear association between RUNX family expression and ESTIMATE score, RNA stemness, and DNA stemness scores. Compared with RUNX1 and RUNX2, RUNX3 showed relatively low levels of genetic alterations. RUNX family genes had clear associations with immune infiltrate subtypes, and their expression was positively related to immune checkpoint genes and drug sensitivity in most cases. Conclusions: These findings will help to elucidate the potential oncogenic roles of RUNX family genes in different types of cancer and it can function as a prognostic marker in various malignant tumors.

scholarly journals ADAM12 as a Clinical Prognostic Indicator Associated with Tumour Immune Infiltration in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Junfan Pan ◽  
Zhidong Huang ◽  
Yiquan Xu
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Model ◽  
Immune Cell ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Receptor Interaction ◽  
Significant Differential Expression ◽  
Immune Related Genes

Abstract Background: Lung cancer is the most common cause of cancer-related death worldwide. In humans, 22 functional α-disintegrin and metalloproteinases (ADAMs) have been identified, 12 of which have proteolytic activity. The role of ADAMs in cancer has attracted increasing attention. However, the expression and significance of ADAMs in lung adenocarcinoma (LUAD) remain unclear. The current study aimed to explore the expression and prognostic value of ADAM12in LUAD.Methods: The Cancer Genome Atlas(TCGA) database was used to analyse the expression of ADAMs in LUAD. The cBioPortal database was used to obtain and analyse ADAM12 copy number changes, and the LinkedOmics database was utilised for the analysis of ADAM12-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was then performed using TIMER. The relationship between ADAM12 and the tumour immune microenvironment(TIM) was assessed via the TISIDB database. ADAM12 and immune-related genes were used to construct a prognostic model. Knockdown of ADAM12 was performed in vitro in order to verify its biological function. The unpaired t-test was used for comparison between the two groups, ANOVA was used for analysing differences between multiple groups, and the Kaplan-Meier test was used to compare survival between groups.Results: Most ADAMs exhibited significant differential expression in LUAD. ADAM12 expression was significantly higher in LUAD tissues than in healthy tissues, and lower ADAM12 expression was associated with better survival. Genetic alterations of ADAM12 mainly included missense mutations, amplifications, and deep deletions. ADAM12 and positively correlated genes were mainly enriched in protein digestion and absorption, ECM-receptor interaction, and adhesion plaques. ADAM12 had a moderate correlation with immune cell markers EBIP1, CCNB1, EXO1, KNTC1, PRC1 and FAM198B. Prognostic model was established based on ADAM12 and immune-related genes. In vitro experiments revealed that knocking down ADAM12 inhibited cell proliferation, migration and invasion.Conclusion: ADAM12 potentially plays an important role in the occurrence of LUAD and may be utilised as an immunotherapy target and a valuable prognostic biomarker for LUAD.

scholarly journals 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 ◽  
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.

scholarly journals ADAMTS12 acts as a tumor microenvironment related cancer promoter in gastric cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangming Hou ◽  
Yingjuan Xu ◽  
Dequan Wu
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Tumor Promoter ◽  
Protein Protein Interaction ◽  
Oxidative Phosphorylation Pathway ◽  
Cox Proportional Hazard Regression

AbstractThe infiltration degree of immune and stromal cells has been shown clinically significant in tumor microenvironment (TME). However, the utility of stromal and immune components in Gastric cancer (GC) has not been investigated in detail. In the present study, ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cell (TIC) in GC cohort, including 415 cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were screened by Cox proportional hazard regression analysis and protein–protein interaction (PPI) network construction. Then ADAMTS12 was regarded as one of the most predictive factors. Further analysis showed that ADAMTS12 expression was significantly higher in tumor samples and correlated with poor prognosis. Gene Set Enrichment Analysis (GSEA) indicated that in high ADAMTS12 expression group gene sets were mainly enriched in cancer and immune-related activities. In the low ADAMTS12 expression group, the genes were enriched in the oxidative phosphorylation pathway. CIBERSORT analysis for the proportion of TICs revealed that ADAMTS12 expression was positively correlated with Macrophages M0/M1/M2 and negatively correlated with T cells follicular helper. Therefore, ADAMTS12 might be a tumor promoter and responsible for TME status and tumor energy metabolic conversion.

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