scholarly journals Elevated expression of IL-10RB acts as an independent unfavorable prognostic marker and predicts the polarization of tumor-associated macrophages in glioma

2021 ◽  
Author(s):  
Yaqiong Fan ◽  
Yichen Peng ◽  
Feng Chen ◽  
Wenbin Li
Keyword(s):  
Immune Responses ◽  
Prognostic Marker ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Cox Regression ◽  
Interleukin 10 ◽  
Immune Checkpoints ◽  
Marker Genes ◽  
Tumor Associated Macrophages ◽  
Cox Regression Analysis

Abstract Background: Interleukin-10 receptor B (IL10RB) is a subunit of the interleukin-10 receptor. As an important part of the interleukin-10 signaling pathway, IL10RB plays an essential role in the regulation of the immune response. However, studies of IL10RB in glioma are rare. The present study aimed to investigate the potential role of IL10RB in glioma.Methods: 611 glioma samples in TCGA dataset and 310 glioma samples in CGGA dataset were download and organized, then analyzed the clinical expression characteristics and prognostic value of IL10RB as well as its correlation with immune cell infiltration in these samples using R. Results: IL10RB expression was significantly higher in the glioma tissues than in the normal tissues and increased in gliomas, especially with malignant phenotype. The Kaplan-Meier survival analysis and Cox regression analysis indicated that IL10RB was significantly associated with poor prognosis in patients with glioma and could be used as an independent prognostic marker. Further functional analysis suggested that IL10RB was involved in immune responses, and high expression of IL10RB in the glioma tissue resulted in more infiltrated immune cells, especially macrophages. Moreover, IL10RB was found to be strongly correlated with marker genes of tumor-associated macrophages (TAMs) and M2 macrophages, but low or even no correlation with marker genes of M1 macrophages. In addition, there was also a significant association between IL10RB and immune checkpoints that suppress effective antitumor immune responses.Conclusions: Our results demonstrated that high expressed IL10RB was associated with the malignant progression of gliomas and poor prognosis, and it might be involved in the polarization of macrophages which play a crucial role in the immunosuppressive response of gliomas.

scholarly journals Prognostic Significance of mRNA Expression RBBP8 or its Methylation in Gliomas

2021 ◽  
Author(s):  
Zhengdong Liu ◽  
Xingbo Cheng ◽  
Yanzheng Gao ◽  
Zhibin Han ◽  
Shaochong Lin ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Set Enrichment Analysis ◽  
Immune Checkpoints ◽  
Low Grade ◽  
Risk Indicator ◽  
Carcinogenic Effect ◽  
Who Grade

Abstract Retinoblastoma-binding protein 8 (RBBP8) affects the prognosis of patients with malignancies through various mechanisms. However, its function in gliomas is unknown. Our study explored the effects of RBBP8 on the prognosis of glioma patients, as well as its regulatory role in the glioma immune microenvironment. We used various bioinformatics methods to analyze the transcriptional profiles and methylation data of RBBP8 in gliomas from multiple databases. Our results showed that the mRNA and protein expression of RBBP8 in gliomas was higher than that in normal tissues and positively correlated with malignant clinical features such as age and WHO grade. A Kaplan–Meier analysis showed that patients with high RBBP8 expression had a poor prognosis. Cox regression demonstrated that RBBP8 was an independent risk indicator and had good diagnostic value for the poor prognosis of glioma. A meta-analysis confirmed the carcinogenic effect of RBBP8 on glioma, while the Tumor Immune Estimation Resource analysis showed that RBBP8 was positively correlated with the infiltration of six immune cell types in low-grade glioma, but only with dendritic cells in glioblastoma multiforme. Importantly, RBBP8 was positively correlated with many well-known immune checkpoints (e.g., CTLA4 and PDL-1). Finally, a gene set enrichment analysis revealed that RBBP8 can promote the activation of cancer-related pathways such as cell cycle, DNA replication and so on. In conclusion, this study is the first to elaborate on the value of RBBP8 in the pathological process of glioma for anti-tumor immunotherapy. In addition, the expression of RBBP8 and its methylation site, cg05513509, may provide potential targets for glioma therapy.

Comprehensive Analysis of the Immune Effect of TGFβ1 in Colorectal Adenocarcinoma:A TGFβ1-related Prognostic Model of Tumor Microenvironment

2021 ◽  
Author(s):  
Yucheng Qian ◽  
Lina Zhang ◽  
Jihang Wen ◽  
Yanxia Mei ◽  
Jingsun Wei ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Survival Data ◽  
Prognostic Model ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Immune Checkpoints ◽  
Cox Regression Analysis

Abstract ColorColorectal cancer is one of the most common cancer worldwide. Recently, tumor microenvironment (TME), especially its remoulding , is thought to control the colorectal cancer genesis and progression. In this study, we use ESTIMATEscore to make out the proportion of immune and stromal components in colorectal adenocarcinoma (CRA) samples from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were found by COX regression analysis and protein-protein interaction (PPI) network, among which TGFβ1 was supposed to be a prognosis factor and tumor environment indicator. Continuous analysis showed that TGFβ1 expression is positively correlated with lymph node metastasis (N stage) but negatively correlated with survival. Gene Set Enrichment Analysis (GSEA) revealed that the genes of the high-expression TGFβ1 group were mainly enriched in immune-related activities. Cluster analysis divided the samples into 2 subgroups. 24 HLA-related genes and 8 immune checkpoint genes were found upregulated in the high immunity group as well as TGFβ1, which suggests the possibility of novel therapies targeting immune checkpoints combined with TGFβ1. Tumor-infiltrating immune cell (TIC) profile of CRA patients was described by CIBERSORT analysis. Further analysis showed that the infiltration of Tregs and Neutrophils were positively correlated with TGFβ1 high expression. Then 3 TGFβ1-related genes were picked out to construct a prognostic model, which matches the survival data well.

scholarly journals Molecular Characteristics, Clinical Implication, and Cancer Immunity Interactions of Pyroptosis-Related Genes in Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Dandan Xu ◽  
Zhipeng Ji ◽  
Ling Qiang
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Signature ◽  
Immune Checkpoints ◽  
Molecular Characteristics ◽  
Predictive Index ◽  
Cox Regression Analysis ◽  
Cancer Immunity ◽  
Tcga Dataset

Objective: Pyroptosis represents an emerging inflammatory form of programmed cell death. Herein, specific functions and clinical implications of pyroptosis-related genes were systematically characterized in breast cancer.Methods: Expression, somatic mutation and copy number variation of 33 pyroptosis-related genes were assessed in breast cancer from TCGA dataset. Their interactions, biological functions and prognostic values were then observed. By stepwise Cox regression analysis, a pyroptosis-related gene signature was generated. The predictive efficacy in survival was examined by survival analyses, ROCs, univariate and multivariate analyses and subgroup analyses. Associations between risk score (RS) and cancer immunity cycle, HLA, immune cell infiltrations, and immune checkpoints were analyzed.Results: Most of pyroptosis-related genes were abnormally expressed in breast cancer. CASP8, NLRC4, NLRP3, NLRP2, PLCG1, NLRP1, NLRP7, SCAF11, GSDMC, and NOD1 occurred somatic mutations as well as most of them had high frequency of CNV. There were closely interactions between them. These genes were distinctly enriched in immune-related processes. A three-gene signature was generated, containing IL-18, GSDMC, and TIRAP. High RS predicted poorer overall survival, progression, and recurrence. After verification, this RS was an independent and sensitive predictive index. This RS was negatively correlated to cancer immunity cycle. Also, low RS was characterized by high HLA, immune cell infiltrations and immune checkpoints. A nomogram including age and RS was generated for accurately predicting 5-, 8-, and 10-year survival probabilities.Conclusion: Pyroptosis-related genes exert key roles in cancer immunity and might be applied as a prognostic factor of breast cancer.

scholarly journals An Immune-Related Gene Prognostic Index for Triple-Negative Breast Cancer Integrates Multiple Aspects of Tumor-Immune Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5342
Author(s):  
Xiaowei Wang ◽  
Wenjia Su ◽  
Dabei Tang ◽  
Jing Jing ◽  
Jing Xiong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Molecular Taxonomy ◽  
Prognostic Index ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Data Set ◽  
Cox Regression Analysis

Tumor-immune cell compositions and immune checkpoints comprehensively affect TNBC outcomes. With the significantly improved survival rate of TNBC patients treated with ICI therapies, a biomarker integrating multiple aspects of TIME may have prognostic value for improving the efficacy of ICI therapy. Immune-related hub genes were identified with weighted gene co-expression network analysis and differential gene expression assay using The Cancer Genome Atlas TNBC data set (n = 115). IRGPI was constructed with Cox regression analysis. Immune cell compositions and TIL status were analyzed with CIBERSORT and TIDE. The discovery was validated with the Molecular Taxonomy of Breast Cancer International Consortium data set (n = 196) and a patient cohort from our hospital. Tumor expression or serum concentrations of CCL5, CCL25, or PD-L1 were determined with immunohistochemistry or ELISA. The constructed IRGPI was composed of CCL5 and CCL25 genes and was negatively associated with the patient’s survival. IRGPI also predicts the compositions of M0 and M2 macrophages, memory B cells, CD8+ T cells, activated memory CD4 T cells, and the exclusion and dysfunction of TILs, as well as PD-1 and PD-L1 expression of TNBC. IRGPI is a promising biomarker for predicting the prognosis and multiple immune characteristics of TNBC.

scholarly journals Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma

2022 ◽  
Vol 8 ◽  
Author(s):  
Fengfeng Wu ◽  
Juntao Xu ◽  
Mingchao Jin ◽  
Xuesheng Jiang ◽  
Jianyou Li ◽  
...  
Keyword(s):  
Risk Score ◽  
Immune Cell ◽  
Cox Regression ◽  
External Validation ◽  
Gene Signature ◽  
Low Risk ◽  
Immune Checkpoints ◽  
Survival Duration ◽  
Cox Regression Analysis ◽  
Chemotherapy Drugs

Objective: Hypoxic tumors contribute to local failure and distant metastases. Nevertheless, the molecular hallmarks of hypoxia remain ill-defined in osteosarcoma. Here, we developed a hypoxic gene signature in osteosarcoma prognoses.Methods: With the random survival forest algorithm, a prognostic hypoxia-related gene signature was constructed for osteosarcoma in the TARGET cohort. Overall survival (OS) analysis, receiver operating characteristic (ROC) curve, multivariate cox regression analysis, and subgroup analysis were utilized for assessing the predictive efficacy of this signature. Also, external validation was presented in the GSE21257 cohort. GSEA was applied for signaling pathways involved in the high- and low-risk samples. Correlation analyses between risk score and immune cells, stromal/immune score, immune checkpoints, and sensitivity of chemotherapy drugs were performed in osteosarcoma. Then, a nomogram was built by integrating risk score, age, and gender.Results: A five-hypoxic gene signature was developed for predicting survival outcomes of osteosarcoma patients. ROC curves confirmed that this signature possessed the well predictive performance on osteosarcoma prognosis. Furthermore, it could be independently predictive of prognosis. Metabolism of xenobiotics by cytochrome P450 and nitrogen metabolism were activated in the high-risk samples while cell adhesion molecules cams and intestinal immune network for IgA production were enriched in the low-risk samples. The low-risk samples were characterized by elevated immune cell infiltrations, stromal/immune scores, TNFRSF4 expression, and sensitivity to cisplatin. The nomogram accurately predicted 1-, 3-, and 5-years survival duration.Conclusion: These findings might offer an insight into the optimization of prognosis risk stratification and individualized therapy for osteosarcoma patients.

scholarly journals Breakthrough Mucormycosis Developing on Mucorales-Active Antifungals Portrays a Poor Prognosis in Patients with Hematologic Cancer

2021 ◽  
Vol 7 (3) ◽  
pp. 217
Author(s):  
Dierdre B. Axell-House ◽  
Sebastian Wurster ◽  
Ying Jiang ◽  
Andreas Kyvernitakis ◽  
Russell E. Lewis ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Symptom Onset ◽  
Poor Prognosis ◽  
Treatment Initiation ◽  
Cox Regression ◽  
Severe Neutropenia ◽  
Apache Ii Score ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Cox Regression Analysis

Although breakthrough mucormycosis (BT-MCR) is known to develop on mold-active antifungals without Mucorales activity, it can also occur while on Mucorales-active antifungals. Herein, we retrospectively compared the characteristics and outcomes of patients with hematologic malignancies (HMs) or hematopoietic stem cell transplant (HSCT) who developed BT-MCR on mold-active antifungals with or without Mucorales activity. Of the patients developing BT-MCR, 16 were on Mucorales-active antifungals (9 isavuconazole, 6 posaconazole, 1 amphotericin B), and 87 were on other mold-active agents (52 voriconazole, 22 echinocandins, 8 itraconazole, 5 echinocandin + voriconazole). Both groups were largely comparable in clinical characteristics. Patients developing BT-MCR while on Mucorales-active antifungals had higher 42-day mortality, from either symptom onset (63% versus 25%, p = 0.006) or treatment initiation (69% versus 39%, p = 0.028). In multivariate Cox regression analysis, exposure to Mucorales-active antifungals prior to BT-MCR had a hazard ratio of 2.40 (p = 0.015) for 42-day mortality from treatment initiation and 4.63 (p < 0.001) for 42-day mortality from symptom onset. Intensive care unit (ICU) admission and APACHE II score at diagnosis, non-recovered severe neutropenia, active HM, and amphotericin B/caspofungin combination treatment were additional independent predictors of 42-day mortality. In summary, BT-MCR on Mucorales-active antifungals portrays poor prognosis in HM/HSCT patients. Moreover, improvements in early diagnosis and treatment are urgently needed in these patients.

scholarly journals Expression of LOX Suggests Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p &lt; 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

scholarly journals Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuomao Mo ◽  
Daiyuan Liu ◽  
Dade Rong ◽  
Shijun Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Cancer Genome ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Checkpoints ◽  
Immune Cell Infiltration ◽  
Immunosuppressive Microenvironment

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC.Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score.Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts.Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.

scholarly journals The Prognostic Value of the m6A Score in Multiple Myeloma Based on Machine Learning

2021 ◽  
Vol 1 (3) ◽  
pp. 77-87
Author(s):  
Gong Xiao ◽  
Qiongjing Yuan ◽  
Wei Wang
Keyword(s):  
Multiple Myeloma ◽  
Cancer Progression ◽  
Risk Score ◽  
Prognostic Value ◽  
Risk Model ◽  
Cox Regression ◽  
Microarray Dataset ◽  
Immune Checkpoints ◽  
Bioinformatics Analyses ◽  
Cox Regression Analysis

Background: Multiple myeloma (MM) is one of the most common cancers of the blood system. N6-methyladenosine (m6A) plays an important role in cancer progression. We aimed to investigate the prognostic relevance of the m6A score in multiple myeloma through a series of bioinformatics analyses. Methods: The microarray dataset GSE4581 and GSE57317 used in this study were downloaded from the Gene Expression Omnibus (GEO) database. The m6A score was calculated using the GSVA package. The Random forests, univariate Cox regression analysis and Lasso analyses were performed for the differentially expressed genes (DEGs). Kaplan–Meier analysis and an ROC curve were used to diagnose the effectiveness of the model. Results: The GSVA R software package was used to predict the function. A total of 21 m6A genes were obtained, and 286 DEGs were identified between high and low m6A score groups. The risk model was constructed and composed of PRX, LBR, RB1, FBXL19-AS1, ARSK, MFAP3L, SLC44A3, UNC119 and SHCBP1. Functional analysis of risk score showed that with the increase in the risk score, Activated CD4 T cells, Memory B cells and Type 2 T helper cells were highly infiltrated. Conclusions: Immune checkpoints such as HMGB1, TGFB1, CXCL9 and HAVCR2 were significantly positively correlated with the risk score. We believe that the m6A score has a certain prognostic value in multiple myeloma.

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

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