scholarly journals CRYAB predicts clinical prognosis and is associated with immunocyte infiltration in colorectal cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12578
Author(s):  
Junsheng Deng ◽  
Xiaoli Chen ◽  
Ting Zhan ◽  
Mengge Chen ◽  
Xisheng Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Malignant Tumors ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Gene Marker ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
Advanced Tumor

Background αB-Crystallin (CRYAB) is differentially expressed in various tumors. However, the correlation between CRYAB and immune cell infiltration in colorectal cancer (CRC) remains unclear. Materials & Methods Kaplan–Meier survival curves in The Cancer Genome Atlas (TCGA) were used to evaluate the relationship between CRYAB expression and both overall survival and progression-free survival. The relationships between CRYAB expression and infiltrating immune cells and their corresponding gene marker sets were examined using the TIMER database. Results The expression of CRYAB was lower in CRC tumor tissues than in normal tissues (P < 0.05). High CRYAB gene expression and high levels of CRYAB gene methylation were correlated with high-grade malignant tumors and more advanced tumor, nodes and metastasis (TNM) cancer stages. In addition, in colorectal cancer, there was a positive correlation between CRYAB expression and immune infiltrating cells including neutrophils, macrophages, CD8 + T cells, and CD4 + T cells, as well as immune-related genes including CD2, CD3D, and CD3E. Methylation sites such as cg13084335, cg15545878, cg13210534, and cg15318568 were positively correlated with low expression of CRYAB. Conclusion Because CRYAB likely plays an important role in immune cell infiltration, it may be a potential tumor-suppressor gene in CRC and a potential novel therapeutic target and predictive biomarker for colorectal cancer (CRC).

scholarly journals AEBP1 Predicts Clinical Prognosis and is Associated with Immunocyte Infiltration in Gastric Cancer

2021 ◽  
Author(s):  
Junsheng Deng ◽  
Ting Zhan ◽  
Xiaoli Chen ◽  
Yiyuan Wan ◽  
Mengge Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Cell Infiltration ◽  
Gene Marker ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
The Relationship

Abstract AEBP1 is differentially expressed in various tumors. However, the correlation between AEBP1 and immune cell infiltration in gastric cancer remains unclear. Kaplan-Meier survival curves were used to evaluate the relationship between AEBP1 expression and overall survival and progression-free survival. The relationship between AEBP1 expression and infiltrating immune cells, and their corresponding gene marker sets was examined using the TIMER database.The expression of AEBP1 was lower in gastric cancer (GC) tumor tissues than in normal tissues (P < 0.05). High AEBP1 gene expression and high levels of AEBP1 gene methylation were correlated with high-grade malignant tumor and old TNM stage. In addition, in gastric cancer, there was a positive correlation between AEBP1 expression and immune infiltrating cells, including neutrophils, CD8 + T cells, and CD4 + T cells, as well as immune-related genes, including CD2, CD3D, and CD3E. Methylation sites such as cg00009293, cg08495088, cg12955216, cg10480062, cg06852744 and cg12978582 were positively correlated with low expression of AEBP1. AEBP1 may be a potential tumor suppressor gene in GC and a potential novel therapeutic target and predictive biomarker for GC. AEBP1 likely plays an important role in immune cell infiltration.

scholarly journals SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shaokun Wang ◽  
Li Pang ◽  
Zuolong Liu ◽  
Xiangwei Meng
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
The Relationship

Abstract Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

Crosstalk between the MSI status and tumor microenvironment in colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15236-e15236
Author(s):  
Peng Luo ◽  
Anqi Lin ◽  
Jian Zhang
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Microsatellite Instability ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Immune Microenvironment ◽  
Mutation Data ◽  
Immune Related Genes

e15236 Background: In recent years, cancer immunotherapy has been extensively studied, and colorectal cancer (CRC) patients have also derived clinical benefits from immunotherapy, especially CRC patients with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H), whose sensitivity to immune checkpoint inhibitors (ICIs) is significantly higher than that of patients with microsatellite-stable (MSS)/microsatellite instability-low (MSI-L) disease. This study suggests that patients with MSI-H CRC have a higher mutational burden and more immune cell infiltration than those with MSS/MSI-L disease. However, most studies have not systematically evaluated the immune characteristics and immune microenvironments of MSI-H and MSS/MSI-L CRC. Methods: A published CRC cohort with mutation and immunotherapy-related prognostic data was collected. We analyzed the relationship between the MSI status and prognosis of ICI treatment in an immunotherapy cohort. We then further used mutation data for the immunotherapy and The Cancer Genome Atlas (TCGA)-CRC (colon adenocarcinoma (COAD) + rectum adenocarcinoma (READ) cohorts. For mRNA expression, mutation data analysis of the immune microenvironment and immunogenicity under different MSI status was performed. Results: Compared with MSS/MSI-L CRC patients, patients with MSI-H CRC significantly benefited from ICI treatment. We found that MSI-H CRC had more immune cell infiltration, higher expression of immune-related genes and higher immunogenicity than MSS/MSI-L disease. The MANTIS score used to predict the MSI status was positively correlated with immune cells, immune-related genes, and immunogenicity. In addition, subtype analysis showed that COAD and READ might have different tumor immune microenvironments. Conclusions: MSI-H CRC may have an inflammatory tumor microenvironment and increased sensitivity to ICIs. Unlike those of MSI-H READ, the immune characteristics of MSI-H COAD may be consistent with those of MSI-H CRC. Furthermore, the possible mechanism underlying the prognostic differences among CRC patients receiving ICIs in relation to the immune microenvironment were elucidated to provide theoretical guidance for further improving the curative effect of ICIs treatment on MSI-H CRC patients in the future and solve the problems underlying why MSS/MSI-L CRC patients do not benefit from ICIs treatment.

scholarly journals HILPDA Is a Prognostic Biomarker and Correlates With Macrophage Infiltration in Pan-Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chengdong Liu ◽  
Xiaohan Zhou ◽  
Hanyi Zeng ◽  
Dehua Wu ◽  
Li Liu
Keyword(s):  
Survival Data ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Clinical Prognosis ◽  
Cancer Data ◽  
Tumor Types ◽  
Pan Cancer

Background: The protein hypoxia-inducible lipid droplet-associated (HILPDA) is differentially expressed in various tumors. However, its role and correlation with immune cell infiltration in most tumors remain unclear.Methods: HILPDA expression was analyzed in pan-cancer data from The Cancer Genome Atlas (TCGA) database. The influence of HILPDA in clinical prognosis was evaluated using clinical survival data from TCGA. Enrichment analysis of HILPDA was conducted using the R package “clusterProfiler.” We downloaded the immune cell infiltration score of TCGA samples from published articles and analyzed the correlation between the magnitude of immune cell infiltration and HILPDA expression.Results: HILPDA was highly expressed and associated with worse overall survival, disease-specific survival, and progression-free interval in most tumor types. In addition, HILPDA expression was significantly associated with the glycolysis pathway and infiltration of immune cells. Tumor-associated macrophage (TAM) infiltration increased in tissues with high HILPDA expression in most tumor types. Immunosuppressive genes, such as PD-L1, PD-1, TGFB1, and TGFBR1 were positively correlated with HILPDA.Conclusions: Our study suggests that HILPDA is a marker of poor prognosis. High HILPDA may contribute to TAM infiltration and be associated with tumor immunosuppression status.

scholarly journals Construction and Comprehensive Prognostic Analysis of a lncRNA–miRNA–mRNA Regulatory Network and Tumor Immune Cell Infiltration in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiong Guo ◽  
Xiaolong Liang ◽  
Yujun Wang ◽  
Anqi Cheng ◽  
Chuan Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Prognostic Model ◽  
Immune Cell ◽  
The Cancer Genome Atlas ◽  
Prognostic Models ◽  
Cell Infiltration ◽  
High Morbidity ◽  
Immune Cell Infiltration

Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality worldwide. Recent studies have shown that long noncoding RNAs (lncRNAs) play an important role in almost all human tumors, including CRC. Competitive endogenous RNA (ceRNA) regulatory networks have become hot topics in cancer research. Tumor-infiltrating immune cells (TICs) have also been reported to be closely related to the survival and prognosis of CRC patients. In this study, we used the lncRNA–miRNA–mRNA regulatory network combined with tumor immune cell infiltration to predict the survival and prognosis of 598 CRC patients. First, we downloaded the lncRNA, mRNA, and miRNA transcriptome data of CRC patients from The Cancer Genome Atlas (TCGA) database and identified differentially expressed genes through “limma” package of R software. The ceRNA regulatory network was established by using the “GDCRNATools” R package. Then, univariate Cox analysis and least absolute shrinkage and selection operator analysis were performed to identify the optimal prognostic network nodes, including SRPX, UST, H19, SNHG7, hsa-miR-29b-3p, and TTYH3. Next, we analyzed the differences in 22 types of TICs between 58 normal subjects and 206 CRC patients and included memory CD4 T cells, dendritic cells and neutrophils in the construction of a prognostic model. Finally, we identified the relationship between the ceRNA prognostic model and the infiltrating immune cell prognostic model. In conclusion, we constructed two prognostic models that provide insights on the prognosis and treatment strategy of CRC.

scholarly journals AHSA1 is a Prognostic Biomarker that Correlates with Macrophage Infiltration in Pan-Cancer

2021 ◽  
Author(s):  
Fulei Li ◽  
Chengdong Liu ◽  
Yanling Chen ◽  
Shasha Li ◽  
Lu Bai
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Cancer Data ◽  
Pan Cancer

Abstract Background: Activator of heat shock 90 kDa protein ATPase homolog 1 (AHSA1) is differentially expressed in several tumor types. However, its association with immune cell infiltration remains elusive. Methods: AHSA1 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data and normal tissue expression data from Genotype-Tissue Expression (GTEx). The clinical prognostic role of AHSA1 in pan-cancer was investigated, and an enrichment analysis of AHSA1 was performed using the R package “clusterProfiler.” We downloaded data regarding the immune cell infiltration level of TCGA pan-cancer tissues and analyzed the association between immune cell infiltration and AHSA1 expression. Results: The results of TCGA pan-cancer data analysis revealed that AHSA1 was overexpressed and associated with poor survival in patients with cancer. Furthermore, the infiltration levels of tumor-associated macrophages (TAMs) were higher, while those of CD8+ T cells were lower, in the high AHSA1 expression group. Conclusions: Our study suggests that AHSA1 is an oncogene and a risk factor for patient survival in cancer. AHSA1 may contribute to high infiltration levels of TAMs and low infiltration levels of CD8+ T cells, thus indicating that high AHSA1 expression may be associated with the tumor immunosuppressive microenvironment.

scholarly journals SFTPA1 is a potential prognostic biomarker correlated with immune cell infiltration and response to immunotherapy in lung adenocarcinoma

2021 ◽  
Author(s):  
Lu Yuan ◽  
Xixi Wu ◽  
Longshan Zhang ◽  
Mi Yang ◽  
Xiaoqing Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Lung Adenocarcinoma ◽  
Expression Profile ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Regulatory Pathways ◽  
Chronic Lung Diseases ◽  
Potential Biomarker

AbstractPulmonary surfactant protein A1 (SFTPA1) is a member of the C-type lectin subfamily that plays a critical role in maintaining lung tissue homeostasis and the innate immune response. SFTPA1 disruption can cause several acute or chronic lung diseases, including lung cancer. However, little research has been performed to associate SFTPA1 with immune cell infiltration and the response to immunotherapy in lung cancer. The findings of our study describe the SFTPA1 expression profile in multiple databases and was validated in BALB/c mice, human tumor tissues, and paired normal tissues using an immunohistochemistry assay. High SFTPA1 mRNA expression was associated with a favorable prognosis through a survival analysis in lung adenocarcinoma (LUAD) samples from TCGA. Further GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that SFTPA1 was involved in the toll-like receptor signaling pathway. An immune infiltration analysis clarified that high SFTPA1 expression was associated with an increased number of M1 macrophages, CD8+ T cells, memory activated CD4+ T cells, regulatory T cells, as well as a reduced number of M2 macrophages. Our clinical data suggest that SFTPA1 may serve as a biomarker for predicting a favorable response to immunotherapy for patients with LUAD. Collectively, our study extends the expression profile and potential regulatory pathways of SFTPA1 and may provide a potential biomarker for establishing novel preventive and therapeutic strategies for lung adenocarcinoma.

scholarly journals Enhanced CD4+ and CD8+ T cell infiltrate within convex hull defined pancreatic islet borders as autoimmune diabetes progresses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander J. Dwyer ◽  
Jacob M. Ritz ◽  
Jason S. Mitchell ◽  
Tijana Martinov ◽  
Mohannad Alkhatib ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Convex Hull ◽  
Pancreatic Islets ◽  
Immune Cell ◽  
Nod Mice ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Analytical Strategy ◽  
Islet Mass

AbstractThe notion that T cell insulitis increases as type 1 diabetes (T1D) develops is unsurprising, however, the quantitative analysis of CD4+ and CD8+ T cells within the islet mass is complex and limited with standard approaches. Optical microscopy is an important and widely used method to evaluate immune cell infiltration into pancreatic islets of Langerhans for the study of disease progression or therapeutic efficacy in murine T1D. However, the accuracy of this approach is often limited by subjective and potentially biased qualitative assessment of immune cell subsets. In addition, attempts at quantitative measurements require significant time for manual analysis and often involve sophisticated and expensive imaging software. In this study, we developed and illustrate here a streamlined analytical strategy for the rapid, automated and unbiased investigation of islet area and immune cell infiltration within (insulitis) and around (peri-insulitis) pancreatic islets. To this end, we demonstrate swift and accurate detection of islet borders by modeling cross-sectional islet areas with convex polygons (convex hulls) surrounding islet-associated insulin-producing β cell and glucagon-producing α cell fluorescent signals. To accomplish this, we used a macro produced with the freeware software ImageJ equipped with the Fiji Is Just ImageJ (FIJI) image processing package. Our image analysis procedure allows for direct quantification and statistical determination of islet area and infiltration in a reproducible manner, with location-specific data that more accurately reflect islet areas as insulitis proceeds throughout T1D. Using this approach, we quantified the islet area infiltrated with CD4+ and CD8+ T cells allowing statistical comparison between different age groups of non-obese diabetic (NOD) mice progressing towards T1D. We found significantly more CD4+ and CD8+ T cells infiltrating the convex hull-defined islet mass of 13-week-old non-diabetic and 17-week-old diabetic NOD mice compared to 4-week-old NOD mice. We also determined a significant and measurable loss of islet mass in mice that developed T1D. This approach will be helpful for the location-dependent quantitative calculation of islet mass and cellular infiltration during T1D pathogenesis and can be combined with other markers of inflammation or activation in future studies.

scholarly journals Comprehensive analysis of lncRNA-miRNA-mRNA regulatory networks for microbiota-mediated colorectal cancer associated with immune cell infiltration

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 3410-3425
Author(s):  
Xiangzhou Tan ◽  
Linfeng Mao ◽  
Changhao Huang ◽  
Weimin Yang ◽  
Jianping Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regulatory Networks ◽  
Immune Cell ◽  
Comprehensive Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Development of an Immune-Related Gene Signature for Prognosis in Melanoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Jia-An Zhang ◽  
Xu-Yue Zhou ◽  
Dan Huang ◽  
Chao Luan ◽  
Heng Gu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cell ◽  
Treatment Method ◽  
Gene Signature ◽  
Cell Infiltration ◽  
Venn Diagram ◽  
Immune Cell Infiltration ◽  
Tumor Purity ◽  
New Treatment ◽  
Immune Related Genes

Melanoma remains a potentially deadly malignant tumor. The incidence of melanoma continues to rise. Immunotherapy has become a new treatment method and is widely used in a variety of tumors. Original melanoma data were downloaded from TCGA. ssGSEA was performed to classify them. GSVA software and the "hclust" package were used to analyze the data. The ESTIMATE algorithm screened DEGs. The edgeR package and Venn diagram identified valid immune-related genes. Univariate, LASSO and multivariate analyses were used to explore the hub genes. The "rms" package established the nomogram and calibrated the curve. Immune infiltration data were obtained from the TIMER database. Compared with that of samples in the high immune cell infiltration cluster, we found that the tumor purity of samples in the low immune cell infiltration cluster was higher. The immune score, ESTIMATE score and stromal score in the low immune cell infiltration cluster were lower. In the high immune cell infiltration cluster, the immune components were more abundant, while the tumor purity was lower. The expression levels of TIGIT, PDCD1, LAG3, HAVCR2, CTLA4 and the HLA family were also higher in the high immune cell infiltration cluster. Survival analysis showed that patients in the high immune cell infiltration cluster had shorter OS than patients in the low immune cell infiltration cluster. IGHV1-18, CXCL11, LTF, and HLA-DQB1 were identified as immune cell infiltration-related DEGs. The prognosis of melanoma was significantly negatively correlated with the infiltration of CD4+ T cells, CD8+ T cells, dendritic cells, neutrophils and macrophages. In this study, we identified immune-related melanoma core genes and relevant immune cell subtypes, which may be used in targeted therapy and immunotherapy of melanoma.

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