scholarly journals ANTXR1 Is a Prognostic Biomarker and Correlates With Stromal and Immune Cell Infiltration in Gastric Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiaodong Huang ◽  
Jie Zhang ◽  
Yongbin Zheng
Keyword(s):  
Gastric Cancer ◽  
Clinical Outcomes ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Immune Cell Infiltration ◽  
Mesenchymal Transition ◽  
Response To Chemotherapy

Gastric cancer (GC) is a complex and heterogeneous disease, making it difficult to ascertain the optimal therapeutic approach for individual GC patients. Stromal and immune cell infiltration in GC has a strong correlation with clinical outcomes; however, the underlying mechanisms that drive immunosuppression remain vastly undiscovered. Recent studies validated that anthrax toxin receptor 1 (ANTXR1) is aberrantly expressed in several cancers and holds promise as a new therapeutic target for cancer. However, its immunological roles in GC are still unclear. Here, we show that we identify the distinct stromal and immune cell infiltration in GC between the high and low ANTXR1 expression group by analyzing genomic data. Clinically, ANTXR1 is highly expressed in GC and correlates with adverse clinicopathological characteristics. Additionally, high ANTXR1 expression is linked to markedly poor clinical outcomes and resistance to chemotherapy, whereas the low ANTXR1 expression group is correlated with better outcomes and response to chemotherapy in GC patients. We further revealed the differential landscape of somatic tumor mutation burden (TMB) between the two groups and observed that patients with high ANTXR1 expression suffered from a lower TMB, potentially leading to less sensitivity to checkpoint therapy. Molecularly, results displayed that ANTXR1 is an immunosuppressive element, which may perform its function via promoting the secretion of immunosuppressive factors that play a significant role in modulating tumor-associated fibroblast transformation, M2 macrophage polarization, and T cell exhaustion. Gene set enrichment analysis revealed that cancer-related pathways including epithelial-to-mesenchymal transition, focal adhesion, and transforming growth factor-β (TGF-β) signaling pathways were enriched in high ANTXR1 expression tumors. Our work suggests that ANTXR1 could not only serve as a valuable prognostic biomarker in GC but also be deemed as a potential immunotherapeutic target and useful biomarker of sensitivity to chemotherapy.

PDGFRB is a potential prognostic biomarker and correlated with immune infiltrates in gastric cancer

2021 ◽  
pp. 1-14
Author(s):  
Baohong Liu ◽  
Xingxing Xiao ◽  
Ziqin Lin ◽  
Yongliang Lou ◽  
Lingling Zhao
Keyword(s):  
Gastric Cancer ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Growth Factor Receptor ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Immune Cell Infiltration ◽  
Clinicopathologic Characteristics ◽  
Mortality And Morbidity ◽  
Poor Outcomes

Gastric cancer (GC) is a common cancer with high mortality and morbidity rates worldwide. Although medical and surgical treatments have improved, the mechanisms of the progression of GC remain unclear. Platelet-derived growth factor receptor-β (PDGFRB) plays a pivotal role in angiogenesis and tumor cell proliferation and has been suggested as a prognostic marker of cancer. This study aimed to explore the relationship of PDGFRB expression with clinicopathologic characteristics, immune cell infiltration status, and prognosis in GC. In this study, we visualized the expression and prognostic values of PDGFRB in GC using the Oncomine, UALCAN, GEPIA, and Kaplan-Meier Plotter databases. And then we explored the potential relationships between PDGFRB expression and the levels of immune cell infiltration using the TIMER, GEPIA databases and CIBERSORT algorithm. Furthermore, LinkedOmics analysis was performed to explore the functions for PDGFRB. The results showed close correlations between PDGFRB and immune cell infiltration especially M2 Macrophage infiltration in GC. High PDGFRB expression was related to poor outcomes in GC. High PDGFRB expression can negatively affect GC prognosis by promoting angiogenesis and modulating the tumor immune microenvironment. These results strongly suggest that PDGFRB can be used as a prognostic biomarker of GC and provide novel insights into possible immunotherapeutic targets.

scholarly journals Down-Regulated CLDN10 Predicts Favorable Prognosis and Correlates With Immune Infiltration in Gastric Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
XiongHui Rao ◽  
JianLong Jiang ◽  
ZhiHao Liang ◽  
JianBao Zhang ◽  
ZheHong Zhuang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Her2 Status ◽  
Immune Cell Infiltration ◽  
Cell Markers ◽  
Immune Infiltration

Background: CLDN10, an important component of the tight junctions of epithelial cells, plays a crucial role in a variety of tumors. The effect of CLDN10 expression in gastric cancer, however, has yet to be elucidated.Methods: Differential expression of CLDN10 at the mRNA and protein levels was evaluated using Oncomine, ULCAN, HPA and TIMER2.0 databases. Real-time polymerase chain reaction (RT-PCR) was utilized to further verify the expression of CLDN10 in vitro. Correlations between CLDN10 expression and clinical outcomes of gastric cancer were explored by Kaplan-Meier Plotter. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) were performed via LinkedOmics and GeneMANIA. The correlations between CLDN10 expression and immune cell infiltration and somatic copy number alternations (SCNA) in gastric cancer were explored by TIMER2.0 and GEPIA2.0.Results: CLDN10 expression was lower in gastric cancer compared to adjacent normal tissues, and associated with better prognosis. CLDN10 also showed significant differences at different T stages, Lauren classification, treatments and HER2 status. PPI and GSEA analysis showed that CLDN10 might be involved in signal transmission, transmembrane transport and metabolism. In some major immune cells, low expression of CLDN10 was associated with increased levels of immune cell infiltration. In addition, it was found that different SCNA status in CLDN10 might affect the level of immune cell infiltration. Furthermore, the expression of CLDN10 was significantly associated with the expression of several immune cell markers, especially B cell markers, follicular helper T cell (Tfh) markers and T cell exhaustion markers.Conclusion: Down-regulated CLDN10 was associated with better overall survival (OS) in gastric cancer. And CLDN10 may serve as a potential prognostic biomarker and correlate to immune infiltration levels in gastric cancer.

scholarly journals INHBA is A Novel Prognostic Biomarker And Correlated With Immune Infiltrates In Gastric Cancer

2021 ◽  
Author(s):  
Weifeng Yu ◽  
Zishao Zhong ◽  
Guihua He ◽  
Wang Zhang ◽  
Zhenhao Ye ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Extracellular Matrix ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Curve Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Collagen Formation ◽  
Matrix Organization ◽  
The Impact

Abstract Background: Inhibin subunit beta A (INHBA) is reportedly a potential prognostic biomarker for a variety of cancers. However, its role in gastric cancer (GC) remains elusive. Methods: The expression of INHBA in GC and healthy tissues based on the data obtained from the UCSC Xena database. Logistic regression and Cox regression was performed to explore the correlation between clinical indicators and INHBA expression. Kaplan–Meier curve analysis was performed to assess the impact of INHBA expression on overall survival(OS). In addition, Received operating characteristic curve analysis was implied to clarify the diagnostic role of INHBA in GC. Functional analyses were conducted to explain the potential functions and enrichment pathways for INHBA. TIMER and GEPIA databases were used to calculate the confidence between INHBA and immune cell infiltration in GC. Results: INHBA was upregulated in GC(P < 0.001) and associated with a poor prognosis(P = 0.037). INHBA expression was an independent risk factor for OS(P = 0.004). Additionally, INHBA was a potential diagnostic marker in GC(AUC=0.961) and it was associated with extracellular matrix organization, response to growth factor, and cell-substrate adhesion. Tumor-associated signaling pathways, such as Wnt, Hippo, and p53, were associated with INHBA. Reactome pathways, such as collagen formation and extracellular matrix organization, were significantly enriched. Moreover, high INHBA expression displayed a strong correlation with immune cell infiltration, especially with macrophage infiltration in GC.Conclusions: INHBA could be a potential prognostic biomarker for GC and may drive the abnormal activity of critical cancer-associated pathways, potentially contributing to immune cell infiltration to promote GC development and becoming a new drug target for targeted GC therapies.

scholarly journals C3aR1 Correlates With Immune Cell Infiltration and Serves as Prognostic and Therapeutic Biomarker in Gastric Cancer

2021 ◽  
Author(s):  
weifeng liu ◽  
Zhijie Chu ◽  
Cheng Yang ◽  
Tianbao Yang ◽  
Yanhui Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Differentially Expressed Genes ◽  
Tumor Tissue ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Expression Levels

Abstract As the fourth most common malignancy worldwide, gastric cancer can lead more than 720 000 patient death every year. Precisely therapeutic intervention can significantly improve patients’ survival status underlying the precise clarification by molecular indexes. Identifying the biomarkers highly associated with disease prognosis will be helpful to guide the clinical therapy. C3ar1 is an essential receptor in the complement system, and participates in various biological processes associated with immunological responses. To identify the crucial roles of C3AR1 in gastric cancer tmorigenesis, we determined the mRNA profile, protein expression levels and the clinicopathological indexes using cBioportal, Kaplan-Meier plotter and the Human Protein Atlas databases. To identify the molecular network in C3AR1-expressed gastric cancer, we obtained the differentially expressed genes using the GEPIA database compared with normal stomach tissues. Furthermore, we analyzed the biological impact of these differentially expressed genes using protein-protein interaction network and gene set enrichment analysis, in which we identified the hub genes and critical pathways influenced by over-expressed C3AR1 in gastric cancer. Finally, we evaluated the correlation between the C3AR1 expression levels and immune cell infiltration levels utilizing the Tumor Immunoassay Resource database. Our results revealed that the higher expression level of C3AR1 can lead higher infiltration of T cell CD8+, T cell CD4+, macrophage, neutrophil, B cell and myeloid dendritic cells into tumor tissue. Moreover, we also found that higher infiltration of macrophage cells into tumor tissue can worsen the survival of patients with gastric cancer, which may be highly associated with the polarization states of macrophages (TAM and M2 status). Our investigation suggest that C3AR1 can be as an efficient diagnostic biomarkers for gastric cancer therapy.

scholarly journals Glycolysis-associated lncRNAs identify a subgroup of cancer patients with poor prognoses and a high-infiltration immune microenvironment

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kuo-Hao Ho ◽  
Tzu-Wen Huang ◽  
Chwen-Ming Shih ◽  
Yi-Ting Lee ◽  
Ann-Jeng Liu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Cell ◽  
Molecular Subtypes ◽  
Differentially Expressed Gene ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Mesenchymal Transition ◽  
Cancer Data

Abstract Background Long noncoding (lnc)RNAs and glycolysis are both recognized as key regulators of cancers. Some lncRNAs are also reportedly involved in regulating glycolysis metabolism. However, glycolysis-associated lncRNA signatures and their clinical relevance in cancers remain unclear. We investigated the roles of glycolysis-associated lncRNAs in cancers. Methods Glycolysis scores and glycolysis-associated lncRNA signatures were established using a single-sample gene set enrichment analysis (GSEA) of The Cancer Genome Atlas pan-cancer data. Consensus clustering assays and genomic classifiers were used to stratify patient subtypes and for validation. Fisher’s exact test was performed to investigate genomic mutations and molecular subtypes. A differentially expressed gene analysis, with GSEA, transcription factor (TF) activity scoring, cellular distributions, and immune cell infiltration, was conducted to explore the functions of glycolysis-associated lncRNAs. Results Glycolysis-associated lncRNA signatures across 33 cancer types were generated and used to stratify patients into distinct clusters. Patients in cluster 3 had high glycolysis scores and poor survival, especially in bladder carcinoma, low-grade gliomas, mesotheliomas, pancreatic adenocarcinomas, and uveal melanomas. The clinical significance of lncRNA-defined groups was validated using external datasets and genomic classifiers. Gene mutations, molecular subtypes associated with poor prognoses, TFs, oncogenic signaling such as the epithelial-to-mesenchymal transition (EMT), and high immune cell infiltration demonstrated significant associations with cluster 3 patients. Furthermore, five lncRNAs, namely MIR4435-2HG, AC078846.1, AL157392.3, AP001273.1, and RAD51-AS1, exhibited significant correlations with glycolysis across the five cancers. Except MIR4435-2HG, the lncRNAs were distributed in nuclei. MIR4435-2HG was connected to glycolysis, EMT, and immune infiltrations in cancers. Conclusions We identified a subgroup of cancer patients stratified by glycolysis-associated lncRNAs with poor prognoses, high immune infiltration, and EMT activation, thus providing new directions for cancer therapy.

scholarly journals EPDR1 correlates with immune cell infiltration in hepatocellular carcinoma and can be used as a prognostic biomarker

2020 ◽  
Author(s):  
Ruochan Chen ◽  
Yiya Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Functional Analysis ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Normal Tissues

Abstract Background: Hepatocellular carcinoma (HCC) has high mortality rate and is a serious disease burden globally. Hence, identification and characterization of novel biomarkers for the diagnosis and prognosis of HCC are critically important. The protein EPDR1 (ependymin related 1) is a member of piscine brain glycoproteins and is involved in cell adhesion. This is the first study to report the expression of EPDR1 and its prognostic significance, pathological role, and association with cancer immunity in HCC.Methods: The gene expression, prognostic, and clinicopathological analyses were performed based on the data obtained from multiple transcriptome databases. Protein expression of EPDR1 in HCC was verified using human protein atlas and CPTAC databases. Co-expression network analysis using the LinkedOmics database was performed to identify genes co-expressed with EPDR1 expression. Functional analysis of the co-expressed genes, including gene set enrichment analysis was performed to identify the functional role of EPDR1. The statistical analysis was conducted in R, and the relationship between EPDR1 expression and immune cell infiltration was analyzed using TIMER and CIBERSORT resources. Results: The expression of EPDR1 was found to be significantly higher in HCC tissues than in the normal tissues and is an independent prognostic factor for the overall survival of HCC patients. Further, a high level of EPDR1 was shown to be correlated with advanced stage of HCC. Functional analysis revealed that EPDR1 is associated with multiple signaling pathways as well as pathways related to cancer and apoptosis. Notably, EPDR1 expression significantly correlated with purity and the infiltration levels of B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Further, the EPDR1 expression significantly correlated with the expression of immune signatures, such as KIR2DL4, ITGAM, GATA3, STAT6, STAT5A, BCL6, STAT3, and HAVCR2.Conclusions: Our study identified EPDR1 as a novel prognostic biomarker in HCC. The expression of EPDR1 was shown to be associated with immune cell infiltration as well as the signature molecules that potentially regulate these processes during the carcinogenesis of HCC. With better understanding of its biological function, EPDR1 could become an effective target for HCC diagnosis and treatment in the future.

scholarly journals Immune Landscape of Gastric Carcinoma Tumor Microenvironment Identifies a Peritoneal Relapse Relevant Immune Signature

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuang Zhang ◽  
Danni Li ◽  
Ruoxi Yu ◽  
Ce Li ◽  
Yujia Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Peritoneal Recurrence ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Gene Set Enrichment ◽  
Gene Set

BackgroundGastric cancer (GC) still represents the third leading cause of cancer-related death worldwide. Peritoneal relapse (PR) is the most frequent metastasis occurring among patients with advanced gastric cancer. Increasingly more evidence have clarified the tumor immune microenvironment (TIME) may predict survival and have clinical significance in GC. However, tumor-transcriptomics based immune signatures derived from immune profiling have not been established for predicting the peritoneal recurrence of the advanced GC.MethodsIn this study, we depict the immune landscape of GC by using transcriptome profiling and clinical characteristics retrieved from GSE62254 of Gene Expression Omnibus (GEO). Immune cell infiltration score was evaluated via single-sample gene set enrichment (ssGSEA) analysis algorithm. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to select the valuable immune cells and construct the final model for the prediction of PR. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to check the accuracy of PRIs. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore the molecular pathways associated with PRIs.ResultsA peritoneal recurrence related immune score (PRIs) with 10 immune cells was constructed. Compared to the low-PRIs group, the high-PRIs group had a greater risk. The upregulation of the focal adhesion signaling was observed in the high-PRIs subtype by GSEA and KEGG. Multivariate analysis found that both in the internal training cohort and the internal validation cohort, PRIs was a stable and independent predictor for PR. A nomogram that integrated clinicopathological features and PRIs to predict peritoneal relapse was constructed. Subgroup analysis indicated that the PRIs could obviously distinguish peritoneal recurrence in different molecular subtypes, pathological stages and Lauren subtypes, in which PRIs of Epithelial-Mesenchymal Transitions (EMT) subtype, III-IV stage and diffuse subtype are higher respectively.ConclusionOverall, we performed a comprehensive evaluation of the immune landscape of GC and constructed a predictive PR model based on the immune cell infiltration. The PRIs represents novel promising feature of predicting peritoneal recurrence of GC and sheds light on the improvement of the personalized management of GC patients after surgery.

scholarly journals Bioinformatics Analysis of C3 in Brain Low Grade Gliomas as Potential Therapeutic Target and Promoting Immune Cell Infiltration

2021 ◽  
Author(s):  
Xiujuan wu ◽  
Siyi Wu ◽  
Kaiting Miao ◽  
Lijing Wang ◽  
Yuanyuan Ma
Keyword(s):  
Cell Cycle ◽  
Immune Cell ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Mesenchymal Transition ◽  
Low Grade Gliomas ◽  
Regulation Of Cell Cycle ◽  
The Impact

Abstract Background Low grade gliomas is the malignant nervous tumor with distinct biological and clinical characteristics. Despite advances in diagnostic and therapeutic methods, how to significantly elongate the survival of low grade gliomas is still the challenge. Complement 3, as the critical component in the innate immune system, play an essential role in local immune response and participated into the regulation of the epithelial-mesenchymal transition and tumor microenvironment. Methods In this study, we systematically determined the expression levels of C3 in low grade gliomas using various public databases. Then, we further identified the impact of C3 expression on immune cell infiltration compared to normal tissue, indicating the effect of cellular microenvironment on overall survival of LGG patients. Results We obtained transcriptional and survival of C3 in LGG from GEPIA and cBioportal database, and the differentially expressed genes were obtained. By performing the analysis of GO and protein-protein interaction network, we have identified the top-ranked 10 hub genes, which are highly associated with regulation of cell cycle. The gene set enrichment analysis demonstrated that overexpression of C3 in LGG patient is positively correlated with regulation of cell cycle. Finally, the immune cell infiltration of C3 in LGG patients was employed and clearly showed that higher neutrophil infiltration can worsen the survival of LGG patients with higher C3 expression. These results were confirmed by the Human Protein Atlas database, in which expression level of C3 protein in gliomas patients always higher. Conclusions This investigation implied that C3 can be as the potential targets of precise therapy for patient with low grade gliomas.

scholarly journals Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages

2020 ◽  
Vol 9 (5) ◽  
pp. 1430 ◽  
Author(s):  
Ji Young Kang ◽  
Minchan Gil ◽  
Kyung Eun Kim
Keyword(s):  
Mrna Expression ◽  
Clinical Relevance ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Treg Cells ◽  
Cell Infiltration ◽  
M2 Macrophage ◽  
Immune Cell Infiltration ◽  
Stomach Adenocarcinoma

Neuropilin1 (NRP1) plays a critical role in tumor progression and immune responses. Although the roles of NRP1 in various tumors have been investigated, the clinical relevance of NRP1 expression in stomach adenocarcinoma (STAD) has not been studied. To investigate the use of NRP1 as a prognostic biomarker of STAD, we analyzed NRP1 mRNA expression and its correlation with patient survival and immune cell infiltration using various databases. NRP1 mRNA expression was significantly higher in STAD than normal tissues, and Kaplan-Meier survival analysis showed that NRP1 expression was significantly associated with poor prognosis in patients with STAD. To elucidate the related mechanism, we analyzed the correlation between NRP1 expression and immune cell infiltration level. In particular, the infiltration of immune-suppressive cells, such as regulatory T (Treg) cells and M2 macrophage, was significantly increased by NRP1 expression. In addition, the expression of interleukin (IL)-35, IL-10, and TGF-β1 was also positively correlated with NRP1 expression, resulting in the immune suppression. Collectively in this study, our integrated analysis using various clinical databases shows that the significant correlation between NRP1 expression and the infiltration of Treg cells and M2 macrophage explains poor prognosis mechanism in STAD, suggesting the clinical relevance of NRP1 expression as a prognostic biomarker for STAD patients.

Sign in / Sign up

Export Citation Format

Share Document