Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas

BackgroundColon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation.MethodsThe differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms.ResultsBGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients.ConclusionBGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.

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ANXA2 is correlated with the molecular features and clinical prognosis of glioma, and acts as a potential marker of immunosuppression

Scientific Reports ◽

10.1038/s41598-021-00366-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kaiming Ma ◽

Xin Chen ◽

Weihai Liu ◽

Yang Yang ◽

Suhua Chen ◽

...

Keyword(s):

Immune Response ◽

Poor Prognosis ◽

Suppressor Cells ◽

High Grade Glioma ◽

The Cancer Genome Atlas ◽

Clinical Value ◽

Clinical Prognosis ◽

Molecular Features ◽

Potential Marker ◽

Genome Atlas

AbstractRecent studies have shown that ANXA2 is important in the development of many cancers, while its role in glioma-related immune response remains unclear. We aimed to comprehensively investigate its biological characteristics and clinical value in glioma. We analyzed 699 glioma samples from The Cancer Genome Atlas as training cohort and 325 samples from the Chinese Glioma Genome Atlas as validation cohort. All the statistical analyses and figures were generated with R. ANXA2 was overexpressed significantly in high-grade glioma, isocitrate dehydrogenase wild-type and mesenchymal-subtype glioma. ANXA2 was a special indicator of mesenchymal subtype. The survival analysis showed that highly-expressed ANXA2 was related to worse survival status as an independent factor of poor prognosis. Further gene ontology analysis showed that ANXA2 was mainly involved in immune response and inflammatory activities of glioma. Subsequent correlation analysis showed that ANXA2 was positively correlated with HCK, LCK, MHC II, STAT1 and interferon but negatively with IgG. Meanwhile, ANXA2 was positively related to the infiltration of tumor-related macrophages, regulatory T cells and myeloid-derived suppressor cells. Our study revealed that ANXA2 is a biomarker closely related to the malignant phenotype and poor prognosis of glioma, and plays an important role in immune response, inflammatory activity and immunosuppression.

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Immune and clinical features of CD96 expression in glioma by large-scale analysis

10.21203/rs.2.23546/v1 ◽

2020 ◽

Author(s):

Qiang Zhang ◽

Hua Zhong ◽

Yinchun Fan ◽

Qian Liu ◽

Jiancheng Song ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Large Scale ◽

The Cancer Genome Atlas ◽

Immune Checkpoints ◽

Immune Functions ◽

Clinical Prognosis ◽

Regulatory Pathways ◽

Cox Analysis ◽

Genome Atlas

Abstract Background: Immune checkpoints target regulatory pathways in T cells which enhance antitumor immune responses and elicit durable clinical responses . As a novel immune checkpoint, CD96 is an attractive key target for cancer immunotherapy. However, there is no integrative investigation of CD96 in glioma. Our study explored the relationship between CD96 expression and clinical prognosis in glioma. Methods: A total of 1,024 RNA and clinical data were enrolled in this study, including 325 samples from the Chinese Glioma Genome Atlas (CGGA) database and 699 samples from The Cancer Genome Atlas (TCGA) dataset. R language was used to perform statistical analysis and draw figures. Results: CD96 had a consistently positive relationship with glioblastoma and highly enriched in IDH-wildtype and mesenchymal subtype glioma. GO enrichment and GSVA analyses suggested that CD96 was more involved in immune functions, especially related to T cell-mediated immune response in glioma. Subsequent immune infiltration analysis manifes ted that CD96 was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages , neutrophils, and DCs in GBM and LGG. Additionally, CD96 was tightly associated with other immune checkpoints including PD-1 , CTLA-4 , TIGIT , and TIM-3 . Univariate and multivariate Cox analysis demonstrated that CD96 acts as an independent indicator of poor prognosis in glioma. Conclusion: CD96 expression was increased in malignant phenotype and negatively associated with overall survival (OS) in glioma. CD96 also showed a positive correlation with other immune checkpoints, immune response, and inflammatory activity. Our findings indicate that CD96 is a promising clinical target for further immunotherapeutic in glioma patients.

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Bioinformatic Analysis of Immune Significance of RYR2 Mutation in Breast Cancer

BioMed Research International ◽

10.1155/2021/8072796 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Zhiquan Xu ◽

Ling Xiang ◽

Rong Wang ◽

Yongfu Xiong ◽

He Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Immune Response ◽

T Cells ◽

Immune Cell ◽

Cox Regression ◽

Cancer Genome ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Specific Gene ◽

Clinical Prognosis

Background. Currently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in BC are not fully understood. Methods. Comprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor-infiltrating immune cell fractions. Results. We analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation-enriched signaling pathways were related to immune-associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages. Conclusion. RYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.

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ANXA2 is Correlated With the Molecular Features and Clinical Prognosis of Glioma, and Acts as a Potential Marker of Immunosuppression

10.21203/rs.3.rs-665909/v1 ◽

2021 ◽

Author(s):

Kaiming Ma ◽

Xin Chen ◽

Weihai Liu ◽

Yang Yang ◽

Suhua Chen ◽

...

Keyword(s):

Immune Response ◽

Suppressor Cells ◽

High Grade Glioma ◽

The Cancer Genome Atlas ◽

Sequencing Data ◽

Clinical Value ◽

Clinical Prognosis ◽

Molecular Features ◽

Potential Marker ◽

Genome Atlas

Abstract Background: Recent studies have shown that ANXA2 plays a crucial role in the development of many cancers, while its role in glioma remains unclear. Thus, our study aimed to investigate the molecular biological characteristics and clinical value of ANXA2 in glioma. Methods: We analyzed the RNA sequencing data of 325 glioma samples from the Chinese Glioma Genome Atlas (CGGA) as the training cohort and the RNA expression data of 699 samples from The Cancer Genome Atlas (TCGA) database as the validation cohort, totaling approximately 1024 samples. Results: We found that ANXA2 was overexpressed significantly in high-grade glioma (HGG), isocitrate dehydrogenase (IDH) wild-type glioma and mesenchymal-subtype glioma. Receiver operating characteristic (ROC) analysis revealed that ANXA2 was a potential indicator of the mesenchymal subtype. Kaplan–Meier curve analysis revealed that high expression of ANXA2 indicated significantly poorer survival in glioma and HGG patients. Multivariate Cox analysis also demonstrated that ANXA2 acted as an independent indicator of poor prognosis in glioma patients. Further gene ontology (GO) analysis showed that ANXA2-related genes were mainly involved in the innate immune response and inflammatory response of glioma, and these genes were positively correlated with the expression of ANXA2. Then, we selected seven immune-related meta-genes and found that ANXA2 was positively correlated with HCK, LCK, MHC II, STAT1 and interferon but negatively correlated with IgG. Subsequent correlation analysis of infiltrating immune cells showed that ANXA2 was positively correlated with the infiltration of tumor-related macrophages (TAMs), regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), suggesting that ANXA2 may be involved in the immunosuppression of glioma.Conclusion: Our study revealed that ANXA2 is closely related to the malignant glioma phenotype and poor patient prognosis. ANXA2 also plays an important role in the immune response and inflammatory activity and can be considered a biomarker of immunosuppression in glioma. These findings suggest that ANXA2 may be a promising target for the further development of immunotherapeutic for glioma.

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Immunological aspects of coronavirus disease during pregnancy: an integrative review

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.66.5.696 ◽

2020 ◽

Vol 66 (5) ◽

pp. 696-700 ◽

Cited By ~ 2

Author(s):

Camila Radelley Azevedo Costa da Silva ◽

Lisiane Vital de Oliveira ◽

Lorenna Peixoto Lopes ◽

Wancler Albert Gomes dos Santos ◽

Isabela Karine Rodrigues Agra

Keyword(s):

Immune Response ◽

Pregnant Women ◽

Scientific Evidence ◽

Integrative Review ◽

Clinical Prognosis ◽

Th2 Immune Response ◽

Potential Contributor ◽

Inflammatory State ◽

Immune Imbalance ◽

In Pregnancy

SUMMARY OBJECTIVE To review the immunological aspects of the 2019 coronavirus disease (COVID-19) in pregnancy, based on the scientific evidence currently available. METHODS An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed) and LILACS databases, using the descriptors “pregnancy” and “COVID-19”. This search included articles published up until 14th April 2020 published in English, Spanish or Portuguese. After reading the articles available in their entirety, those related specifically to the immunological aspects of the disease in pregnancy were selected. We initially found a total of 62 articles; 52 were accessed in full-text, and 5 were finally selected. RESULTS Pregnant women are more affected by respiratory diseases possibly because of physiological, immune, and anatomical changes. Some studies highlight the important shift to a T-helper lymphocyte type 2 (Th2) immune response in pregnancy, as a potential contributor to the severity in cases of COVID-19. Additionally, the cytokine storm present in severe cases leads to an increased inflammatory state, which may deteriorate the clinical prognosis in this population. Therefore, pregnant women may represent a vulnerable group to COVID-19 infection, primarily due to the immune imbalance in the maternal-fetal interface. CONCLUSION Maternal immune response probably plays an important role in the pathophysiology of this infection, although some details remain unsolved. Although further studies are needed to deeply investigate the immunological aspects of the disease in pregnancy, our findings may provide insights into the possible immune mechanisms involved in the pathophysiology of COVID-19 in pregnancy.

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