scholarly journals METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhipeng Jiang ◽  
Wen Yin ◽  
Hecheng Zhu ◽  
Jun Tan ◽  
Youwei Guo ◽  
...  
Keyword(s):  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Biomarker ◽  
Disease Free Survival ◽  
Cell Infiltration ◽  
Lower Grade ◽  
Immune Cell Infiltration ◽  
Mesenchymal Transition ◽  
Lower Grade Glioma ◽  
Cancer Types

AbstractMethyltransferase-like 7B (METTL7B) is a member of the methyltransferase-like protein family that plays an important role in the development and progression of tumors. However, its prognostic value and the correlation of METTL7B expression and tumor immunity in some cancers remain unclear. By analyzing online data, we found that METTL7B is abnormally overexpressed in multiple human tumors and plays an important role in the overall survival (OS) of patients with 8 cancer types and disease-free survival (DFS) of patients with 5 cancer types. Remarkably, METTL7B expression was positively correlated with the OS and DFS of patients with lower-grade glioma (LGG). In addition, a positive correlation between METTL7B expression and immune cell infiltration in LGG was observed. Moreover, we identified a strong correlation between METTL7B expression and immune checkpoint gene expression in kidney chromophobe (KICH), LGG and pheochromocytoma and paraganglioma (PCPG). Furthermore, METTL7B was involved in the extracellular matrix (ECM) and immune-related pathways in LGGs. Finally, in vitro experiments showed that knockdown of METTL7B inhibited the growth, migration, invasion and the epithelial–mesenchymal transition (EMT) of LGG cells. METTL7B expression potentially represents a novel prognostic biomarker due to its significant association with immune cell infiltration in LGG.

scholarly journals Association Between Tumor Mutation Burden and Prognosis in Lower-Grade Glioma: An Exploratory Study 

2021 ◽  
Author(s):  
Di Cao ◽  
Jun Wang ◽  
Yan Lin ◽  
Guangwei Li
Keyword(s):  
Immune Cell ◽  
Differential Expression Analysis ◽  
Cell Infiltration ◽  
Lower Grade ◽  
Immune Cell Infiltration ◽  
Hub Genes ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Lower Grade Glioma ◽  
Genome Atlas

Abstract Background: The therapeutic efficacy of immune checkpoint inhibitor therapy is highly influenced by tumor mutation burden (TMB). The relationship between TMB and prognosis in lower-grade glioma is still unclear. We aimed to explore the relationships and mechanisms between them in lower-grade glioma.Methods: We leveraged somatic mutation data from The Cancer Genome Atlas (TCGA). Clinical cases were divided into high- and low-TMB groups based on the median of TMB. Infiltrating immune cells were analyzed using CIBERSORT and differential expression analysis between the prognostic groups performed. The key genes were identified as intersecting between immune-related genes. Cox regression and survival analysis were performed on the intersecting genes. A total of 7 hub genes were identified. The effect of somatic copy number alterations (SCNA) of the hub genes on immune cell infiltration was analyzed using TIMER, which was used to determine the risk factors and immune infiltration status in LGG. Subsequently, based on hub genes, a TMB Prognosis Index (TMBPI) model was constructed to predict the risk in LGG patients. Besides, this model was validated using data from TCGA and Chinese Glioma Genome Atlas (CGGA).Results: High-TMB favored worse prognosis (P＜0.001) and macrophage infiltration was an independent risk factor (P＜0.001). In the high-TMB group (P=0.033, P=0.009), the proportion of macrophages M0 and M2 increased and monocytes decreased (P=0.006). Besides, the SCNA of the hub genes affected the level of immune cell infiltration by varying degrees among which IGF2BP3, NPNT, and PLA2G2A had a significant impact. The AUC of the ROC curve at 1-, 3- and 5-years were all above 0.74.Conclusions: This study implies that high-TMB correlated with unfavorable prognosis in lower-grade glioma. And high-TMB may have an impact on prognosis by changing tumor microenvironment, caused by the SCNAs of genes. The TMBPI model accurately predicted prognosis in LGG patients.

Mechanisms underlying the association between sarcopenia and poor oncologic outcomes in clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 662-662
Author(s):  
Alejandro Sanchez ◽  
Fengshen Kuo ◽  
Stacey Petruzella ◽  
Oguz Akin ◽  
Michael Paris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Oncologic Outcomes ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
International Consensus ◽  
Mesenchymal Transition

662 Background: Sarcopenia (low skeletal muscle mass) is associated with poor outcomes in patients with ccRCC. The mechanisms underlying this association are unclear. To understand this association, we examined gene expression differences by sarcopenic status in patients with ccRCC. Methods: The cohort consisted of 62 ccRCC patients treated by nephrectomy and previously transcriptomically-profiled in the Cancer Genome Atlas. Computed tomography scans without contrast performed within two months of surgery were reviewed to determine skeletal muscle cross-sectional area. Sarcopenia (yes/no) was defined according to gender-specific international consensus definitions. Baseline differences in clinicopathologic characteristics were assessed using the Chi-squared test for categorical and t-test for continuous variables. Differential expression analyses were performed using the R package “DESeq2.” Gene set enrichment analyses (GSEA) and single-set GSEA were used to evaluate differences in MSigDB Hallmark gene sets and estimate immune cell infiltration, respectively. P-values were corrected for multiple testing (p-adjust). Results: The cohort was predominantly male (82%), white (97%) and had localized disease (58%). Median age was 58.9 years (SD: 12.1). Sarcopenic (47%) patients were older (p < 0.001), obese (p < 0.001), and presented with higher AJCC stage (p = 0.006). In primary tumor specimens, sarcopenic patients demonstrated increased expression of angiogenic, inflammatory (e.g., IL-6, TNF-alpha), and epithelial mesenchymal transition programs (p-adjust < 0.05). Furthermore, sarcopenic patients had higher macrophage (p = 0.003) and Th17 immune cell infiltration (p = 0.003). Conclusions: Our findings suggest that ccRCC patients who are sarcopenic harbor gene expression programs associated with more aggressive biology. Increased macrophage infiltration and decreased Th17 immune cell infiltration have been previously associated with worse prognosis in ccRCC. It is not clear whether sarcopenia is a cause or consequence of tumor aggressiveness. Validation of these results in a larger cohort of patients and orthogonal validation are ongoing.

scholarly journals PLOD3 Is Associated with Immune Cell Infiltration and Genomic Instability in Colon Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xianyu Deng ◽  
Yun Pan ◽  
Muqing Yang ◽  
Ying Liu ◽  
Jiyu Li
Keyword(s):  
Genomic Instability ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Colon Adenocarcinoma ◽  
Underlying Mechanism ◽  
High Expression ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Tissue Samples ◽  
Mesenchymal Transition

Procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) are a family of enzymes. However, the clinical and functional roles of PLOD3 in colon adenocarcinoma (COAD) have not been investigated. The present study found that PLOD3 was highly upregulated in COAD, which may be resulted from its aberrant DNA methylation. The upregulation of both PLOD3 mRNA and protein was confirmed in our tissue samples. Moreover, high PLOD3 was identified to be associated with unfavorable prognosis in COAD. As genome instability is a hallmark of cancer, PLOD3 was expressed higher in COAD samples with high chromosomal instability (CIN-high) than those with low CIN (CIN-low) and higher in those with low MSI than high MSI, indicating that PLOD3 expression was associated with tumor genomic instability. Furthermore, immune cells showed significantly different infiltrating levels between the high and low PLOD3 expression groups, and the immune score was negatively correlated with PLOD3 expression and higher in samples with low PLOD3 expression, suggesting that high PLOD3 expression was associated with reduced immune cell infiltrating levels in COAD. To further uncover the underlying mechanism of PLOD3 in PLOD3, we compared the COAD samples of high PLOD3 expression with those of low PLOD3 expression and found that high expression of PLOD3 was associated with reduced expression of immune regulators and enhanced activities of two tumor-promoting pathways, including gluconeogenesis and TGF-beta signaling in epithelial-mesenchymal transition (EMT), suggesting that high expression of PLOD3 causes poor prognosis in COAD by weakening the immune cell infiltration and enhancing activities of tumor-promoting pathways. In summary, the present study highlights the importance of PLOD3 and provides the evidence about the functional role of PLOD3 in COAD.

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.

scholarly journals Identification of SHMT2 as a Potential Prognostic Biomarker and Correlating with Immune Infiltrates in Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lianxiang Luo ◽  
Yushi Zheng ◽  
Zhiping Lin ◽  
Xiaodi Li ◽  
Xiaoling Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Methyl Transferase ◽  
Cox Proportional Hazard Regression

It has attracted growing attention that the role of serine hydroxy methyl transferase 2 (SHMT2) in various types of cancers. However, the prognostic role of SHMT2 in lung adenocarcinoma (LUAD) and its relationship with immune cell infiltration is not clear. In this study, the information of mRNA expression and clinic data in LUAD were, respectively, downloaded from the GEO and TCGA database. We conducted a biological analysis to select the signature gene SHMT2. Online databases including Oncomine, GEPIA, TISIDB, TIMER, and HPA were applied to analyze the characterization of SHMT2 expression, prognosis, and the correlation with immune infiltration in LUAD. The mRNA expression and protein expression of SHMT2 in LUAD tissues were higher than in normal tissue. A Kaplan-Meier analysis showed that patients with lower expression level of SHMT2 had a better overall survival rate. Multivariate analysis and the Cox proportional hazard regression model revealed that SHMT2 expression was an independent prognostic factor in patients with LUAD. Meanwhile, the gene SHMT2 was highly associated with tumor-infiltrating lymphocytes in LUAD. These results suggest that the SHMT2 gene is a promising candidate as a potential prognostic biomarker and highly associated with different types of immune cell infiltration in LUAD.

scholarly journals DNASE1L3 as a Prognostic Biomarker Associated with Immune Cell Infiltration in Cancer

2021 ◽  
Vol Volume 14 ◽  
pp. 2003-2017
Author(s):  
Zenghua Deng ◽  
Mengmeng Xiao ◽  
Dexiao Du ◽  
Nan Luo ◽  
Dongfang Liu ◽  
...  
Keyword(s):  
Immune Cell ◽  
Prognostic Biomarker ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Epithelial–mesenchymal Transition Phenotype and Peritumoral Immune Cell Infiltration in Advanced Biliary Tract Cancer

2021 ◽  
Author(s):  
Chung Ryul Oh ◽  
Hyung-Don Kim ◽  
Yeon-Mi Ryu ◽  
Seonmin Lee ◽  
Danbee Kim ◽  
...  
Keyword(s):  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Immune Cell Infiltration ◽  
Mesenchymal Transition ◽  
Tract Cancer ◽  
Survivor Group ◽  
Study Population ◽  
Emt Markers ◽  
Term Survivor ◽  
E Cadherin

Abstract BackgroundWe evaluated the clinical implications of epithelial–mesenchymal transition (EMT) markers and peritumoral immune cell infiltration in patients with biliary tract cancer (BTC) treated with gemcitabine plus cisplatin (GemCis).MethodsForty-five patients with advanced BTC who received GemCis were included as the study population. We conducted multiplex immunohistochemistry and examined EMT markers and their correlations with immune cell infiltrate at the invasive tumor margin. Study population was subdivided into two groups: twenty-four patients with overall survival (OS) less than 10 months (short-term survivor group, SS) and 21 with OS of 20 months or longer (long-term survivor group, LS).ResultsThe density of tumor cells expressing epithelial marker E-cadherin (E-cadherin+ CK+) at the invasive tumor margin tended to be higher in the LS group than in the SS group (p = 0.065). The density of tumor cells expressing mesenchymal marker vimentin (vimentin+ CK+) was significantly higher in the SS group than in the LS group (p = 0.021). Accordingly, the density of E-cadherin- vimentin+ CK+ cells was also significantly higher in the SS group (p = 0.020). The density of OX40 expressing cells (OX40+) was significantly higher in the SS group than in the LS group (p = 0.006). The density of vimentin+ CK+ cells was positively correlated with FoxP3+ CD4+ regulatory T-cells (r = 0.29, p = 0.047) and OX40+ cells (r = 0.48, p < 0.001).ConclusionsEMT-related features were enriched in BTC patients with poor survival outcomes and were associated with the immunosuppressive tumor microenvironment.

scholarly journals KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Lingyue Li ◽  
Yiyu Wang ◽  
Yuan Mou ◽  
Hao Wu ◽  
Ye Qin
Keyword(s):  
Immune Cell ◽  
Prognostic Biomarker ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Th2 Cells ◽  
Th1 Cell ◽  
Transport Pathways ◽  
Epigenetic Factor ◽  
Omics Analysis ◽  
Cancer Types

Background. Lysine-specific demethylase 1A (KDM1A) is a histone demethylation enzyme and a crucial epigenetic factor for multiple pathological pathways that mediate carcinogenesis and immunogenicity. Although increasing evidence supposes the association between KDM1A and cancers, no systematic multi-omics analysis of KDM1A is available. Methods. We systematically evaluated the KDM1A expression of various cancer and normal tissues and the unique relationship between KDM1A expression and prognosis of cancer cases based on The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The genetic variations, phosphorylation, and DNA methylation of KDM1A were analyzed via various tools. We further analyzed the correlation of KDM1A expression and fibroblasts and immune cell infiltration score of TCGA samples via TIMER2.0. Results. KDM1A was highly expressed in 17 types of total 33 cancers, while it expressed low levels in only 4 cancers. High KDM1A expression was associated with worse survival status in various cancers. KDM1A expression was positively correlated with the cancer-associated fibroblasts and myeloid-derived suppressor cells infiltration levels in most cancer types. Additionally, KDM1A in most cancer types was negatively correlated with Th1 cell infiltration and positively correlated with Th2 cells. Moreover, spliceosome, cell cycle, and RNA transport pathways were involved in the functional mechanisms of KDM1A via enrichment analysis. Conclusions. Our study describes the epigenetic factor KDM1A as an oncogene and prognostic biomarker. Our findings provide valuable guidance for further analysis of KDM1A function in pathogenesis and potential clinical treatment.

Profiles of immune‐related genes and immune cell infiltration in the tumor microenvironment of diffuse lower‐grade gliomas

2020 ◽  
Vol 235 (10) ◽  
pp. 7321-7331 ◽  
Author(s):  
Xiangyang Deng ◽  
Dongdong Lin ◽  
Xiaojia Zhang ◽  
Xuchao Shen ◽  
Zelin Yang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Lower Grade ◽  
Immune Cell Infiltration ◽  
Immune Related Genes
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