Identification of Potential Therapeutic Targets and Immune Cell Infiltration Characteristics in Osteosarcoma Using Bioinformatics Strategy

Background. Osteoporosis is characterized by low bone mass, deterioration of bone tissue structure, and susceptibility to fracture. New and more suitable therapeutic targets need to be discovered. Methods. We collected osteoporosis-related datasets (GSE56815, GSE99624, and GSE63446). The methylation markers were obtained by differential analysis. Degree, DMNC, MCC, and MNC plug-ins were used to screen the important methylation markers in PPI network, then enrichment analysis was performed. ROC curve was used to evaluate the diagnostic effect of osteoporosis. In addition, we evaluated the difference in immune cell infiltration between osteoporotic patients and control by ssGSEA. Finally, differential miRNAs in osteoporosis were used to predict the regulators of key methylation markers. Results. A total of 2351 differentially expressed genes and 5246 differentially methylated positions were obtained between osteoporotic patients and controls. We identified 19 methylation markers by PPI network. They were mainly involved in biological functions and signaling pathways such as apoptosis and immune inflammation. HIST1H3G, MAP3K5, NOP2, OXA1L, and ZFPM2 with higher AUC values were considered key methylation markers. There were significant differences in immune cell infiltration between osteoporotic patients and controls, especially dendritic cells and natural killer cells. The correlation between MAP3K5 and immune cells was high, and its differential expression was also validated by other two datasets. In addition, NOP2 was predicted to be regulated by differentially expressed hsa-miR-3130-5p. Conclusion. Our efforts aim to provide new methylation markers as therapeutic targets for osteoporosis to better treat osteoporosis in the future.

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Expression, Prognosis, and Immune Infiltrates Analyses of E2Fs in Human Brain and CNS Cancer

BioMed Research International ◽

10.1155/2020/6281635 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Pan Liao ◽

Shuzhen Han ◽

Honglan Qu

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Immune Cell ◽

Expression Patterns ◽

Therapeutic Targets ◽

Functional Enrichment ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Immune Infiltration ◽

Cns Cancer

Objective. We investigated the expression patterns, potential functions, unique prognostic value, and potential therapeutic targets of E2Fs in brain and CNS cancer and tumor-infiltrating immune cell microenvironments. Methods. We analyzed E2F mRNA expression levels in diverse cancer types via Oncomine and GEPIA databases, respectively. Moreover, we evaluated the prognostic values using GEPIA database and TCGAportal database and the correlation of E2F expression with immune infiltration and the correlation between immune cell infiltration and GBM and LGG prognosis via TIMER database. Then, cBioPortal, GeneMANIA, and DAVID databases were used for mutation analysis, PPI network analysis of coexpressed gene, and functional enrichment analysis. Results. E2F1-8 expression increased in most cancers, including brain and CNS cancer. Higher expression in E2F1, 2, 4, 6, 7, and 8 indicated poor OS of LGG. Higher E2F3–6 and E2F1–8 expressions correlated with poor prognosis and increased immune infiltration levels in CD8+ T cells, macrophages, neutrophils, and DCs in GBM and CD8+ T cells, B cells, CD4+ T cells, neutrophils, macrophages, and DCs in LGG, respectively. Conclusion. E2F1–8 and E2F2–8 could be hopeful prognostic biomarkers of GBM and LGG, respectively. E2F3–6 and E2F1–8 could be likely therapeutic targets in patients with immune cell infiltration of GBM and LGG, respectively.

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WISP1 modulates immune cell infiltration upon drug-induced liver injury (DILI)

Zeitschrift für Gastroenterologie ◽

10.1055/s-0035-1567970 ◽

2015 ◽

Vol 53 (12) ◽

Author(s):

AB Widera ◽

L Pütter ◽

S Leserer ◽

G Campos ◽

K Rochlitz ◽

...

Keyword(s):

Liver Injury ◽

Immune Cell ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Drug Induced ◽

Drug Induced Liver Injury

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Faculty Opinions recommendation of Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725485692.793517744 ◽

2016 ◽

Author(s):

Paul Timpson ◽

Claire Vennin

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Immune Cell ◽

Cancer Invasion ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

Human Breast ◽

Breast Cancer Invasion

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

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02995-4 ◽

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.

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

Scientific Reports ◽

10.1038/s41598-021-96327-2 ◽

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.

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