scholarly journals Pan-Cancer Analyses of Pyroptosis With Functional Implications in Prognosis and Immunotherapy in Cancer

2021 ◽  
Author(s):  
Aibin Liu ◽  
Lin Shen ◽  
Na Li ◽  
Liangfang Shen ◽  
Zhanzhan Li
Keyword(s):  
Cell Death ◽  
The Cancer Genome Atlas ◽  
Dual Roles ◽  
Biological Regulation ◽  
Clinical Prognosis ◽  
Therapy Targets ◽  
Molecular Features ◽  
Cancer Genome Atlas ◽  
Level Model ◽  
Regulator Genes

Abstract Background Programmed cell death is an active and orderly form of cell death regulated by intracellular genes, which plays an important role in the normal occurrence and development of the immune system, and pyroptosis has been found to be involved in the tumorigenesis and development. However, compressive analysis and biological regulation about pyroptosis genes are lack in cancers. Methods Using the data from the The Cancer Genome Atlas, we established a score level model to quantify the pyroptosis level of cancer. Multi-omics bioinformatical analyses was performed to detect pyroptosis-related molecular features and effect of pyroptosis on immunotherapy in cancer. Results In the present study, we performed a comprehensive analysis of pyroptosis and its regulator genes in cancers. Most pyroptosis genes were aberrantly expressed among different cancer types, which is contributed by the CAN frequency and differences of DNA methylation level in cancer. We established the modeling of the pyroptosis level and found that pyroptosis showed dual roles across cancers, while the pyroptosis levels were different in multiple and be significantly associated with clinical prognosis. The dual role of pyroptosis also affect the effects of immunotherapy in several cancers. Multiple pyroptosis genes showed close connections with drug sensitivity across cancers, and may be considered as therapy targets in cancer. Conclusions Our comprehensive analyses provide new insight into the functions of pyroptosis in the initiation, development, and progression and treatment across cancers, suggesting corresponding prognostic and therapeutic utility.

scholarly journals Radiosensitivity index emerges as a potential biomarker for combined radiotherapy and immunotherapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yang-Hong Dai ◽  
Ying-Fu Wang ◽  
Po-Chien Shen ◽  
Cheng-Hsiang Lo ◽  
Jen-Fu Yang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Interferon Γ ◽  
The Cancer Genome Atlas ◽  
Differential Analysis ◽  
Macrophage Polarisation ◽  
Molecular Features ◽  
Kaplan Meier ◽  
M1 Macrophage ◽  
Potential Biomarker ◽  
Cancer Genome Atlas

AbstractIn the era of immunotherapy, there lacks of a reliable genomic predictor to identify optimal patient populations in combined radiotherapy and immunotherapy (CRI). The purpose of this study is to investigate whether genomic scores defining radiosensitivity are associated with immune response. Genomic data from Merged Microarray-Acquired dataset (MMD) were established and the Cancer Genome Atlas (TCGA) were obtained. Based on rank-based regression model including 10 genes, radiosensitivity index (RSI) was calculated. A total of 12832 primary tumours across 11 major cancer types were analysed for the association with DNA repair, cellular stemness, macrophage polarisation, and immune subtypes. Additional 585 metastatic tissues were extracted from MET500. RSI was stratified into RSI-Low and RSI-High by a cutpoint of 0.46. Proteomic differential analysis was used to identify significant proteins according to RSI categories. Gene Set Variance Analysis (GSVA) was applied to measure the genomic pathway activity (18 genes for T-cell inflamed activity). Kaplan-Meier analysis was performed for survival analysis. RSI was significantly associated with homologous DNA repair, cancer stemness and immune-related molecular features. Lower RSI was associated with higher fraction of M1 macrophage. Differential proteomic analysis identified significantly higher TAP2 expression in RSI-Low colorectal tumours. In the TCGA cohort, dominant interferon-γ (IFN-γ) response was characterised by low RSI and predicted better response to programmed cell death 1 (PD-1) blockade. In conclusion, in addition to radiation response, our study identified RSI to be associated with various immune-related features and predicted response to PD-1 blockade, thus, highlighting its potential as a candidate biomarker for CRI.

scholarly journals Novel cancer subtyping method based on patient-specific gene regulatory network

2021 ◽  
Author(s):  
Mai Adachi Nakazawa ◽  
Yoshinori Tamada ◽  
Yoshihisa Tanaka ◽  
Marie Ikeguchi ◽  
Kako Higashihara ◽  
...  
Keyword(s):  
Gene Networks ◽  
Regulatory Networks ◽  
The Cancer Genome Atlas ◽  
Patient Specific ◽  
Specific Gene ◽  
Omics Data ◽  
Cancer Subtypes ◽  
Molecular Systems ◽  
Molecular Features ◽  
Cancer Genome Atlas

The identification of cancer subtypes is important for the understanding of tumor heterogeneity. In recent years, numerous computational methods have been proposed for this problem based on the multi-omics data of patients. It is widely accepted that different cancer subtypes are induced by different molecular regulatory networks. However, only a few incorporate the differences between their molecular systems into the classification processes. In this study, we present a novel method to classify cancer subtypes based on patient-specific molecular systems. Our method quantifies patient-specific gene networks, which are estimated from their transcriptome data. By clustering their quantified networks, our method allows for cancer subtyping, taking into consideration the differences in the molecular systems of patients. Comprehensive analyses of The Cancer Genome Atlas (TCGA) datasets applied to our method confirmed that they were able to identify more clinically meaningful cancer subtypes than the existing subtypes and found that the identified subtypes comprised different molecular features. Our findings show that the proposed method, based on a simple classification using the patient-specific molecular systems, can identify cancer subtypes even with single omics data, which cannot otherwise be captured by existing methods using multi-omics data.

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

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.

scholarly journals Modelling Epithelial Ovarian Cancer in Mice: Classical and Emerging Approaches

2020 ◽  
Vol 21 (13) ◽  
pp. 4806
Author(s):  
Razia Zakarya ◽  
Viive M. Howell ◽  
Emily K. Colvin
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Genetically Engineered ◽  
The Cancer Genome Atlas ◽  
Genetically Engineered Mouse Models ◽  
Molecular Features ◽  
Somatic Gene ◽  
Cancer Genome Atlas ◽  
Serous Epithelial Ovarian Cancer ◽  
Aggressive Subtype

High-grade serous epithelial ovarian cancer (HGSC) is the most aggressive subtype of epithelial ovarian cancer. The identification of germline and somatic mutations along with genomic information unveiled by The Cancer Genome Atlas (TCGA) and other studies has laid the foundation for establishing preclinical models with high fidelity to the molecular features of HGSC. Notwithstanding such progress, the field of HGSC research still lacks a model that is both robust and widely accessible. In this review, we discuss the recent advancements and utility of HGSC genetically engineered mouse models (GEMMs) to date. Further analysis and critique on alternative approaches to modelling HGSC considers technological advancements in somatic gene editing and modelling prototypic organs, capable of tumorigenesis, on a chip.

scholarly journals PABPC1 relevant bioinformatic profiling and prognostic value in gliomas

2020 ◽  
Vol 16 (1) ◽  
pp. 4279-4288 ◽  
Author(s):  
Qiangwei Wang ◽  
Zhiliang Wang ◽  
Zhaoshi Bao ◽  
Chuanbao Zhang ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Biological Process ◽  
The Cancer Genome Atlas ◽  
Analysis Tool ◽  
Expression Data ◽  
Clinical Value ◽  
Mrna Expression Data ◽  
R Language ◽  
Molecular Features ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Aim: We aimed at investigating molecular features and potential clinical value of PABPC1 in gliomas. Materials & methods: We assembled totally 1000 glioma samples with mRNA expression data from Chinese Glioma Genome Atlas and The Cancer Genome Atlas. We utilized R language as the main analysis tool. Gene Ontology was performed for functional analysis. Results: PABPC1 was downregulated in gliomas with higher malignance and PABPC1 may contribute as potential predictor of proneural subtype in gliomas. Higher expression of PABPC1 was significantly related to better prognosis and related to biological process of translation. Conclusion: Our finding improves the understanding of PABPC1 as a novel biomarker with potential therapeutic connotations.

scholarly journals A Novel Ferroptosis-Related lncRNAs Signature Predicts Clinical Prognosis and is Associated with Immune Landscape in Pancreatic Cancer

2021 ◽  
Author(s):  
Haiqin Ping ◽  
Xingqing Jia ◽  
Hengning Ke
Keyword(s):  
Pancreatic Cancer ◽  
Immune Cell ◽  
Pearson Correlation ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Clinical Prognosis ◽  
Pathway Enrichment ◽  
Cancer Genome Atlas ◽  
Pearson Correlation Analysis ◽  
Selection Operator

Abstract Pancreatic cancer is one of the most lethal malignancies and currently therapies are severely lacking. In this study, we aimed to establish a novel ferroptosis-related lncRNAs signature to predict the prognosis of patients with pancreatic cancer and evaluate the predictive abilities of candidate lncRNAs. According to The Cancer Genome Atlas (TCGA) database, a total of 182 patients with pancreatic cancer were included in our study. Ferroptosis-related lncRNAs were screened by Pearson correlation analysis with 60 reported ferroptosis-related genes. Through univariate, least absolute shrinkage and selection operator (LASSO) regression and multivariate regression analyses, a novel signature based on five ferroptosis-related lncRNAs(ZNF236-DT, CASC8, PAN3-AS1, SH3PXD2A-AS1, LINP1) was constructed. Risk-related differentially expressed genes (DEGs) were subjected to enrichment analyses for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.The results revealed that that immune cell infiltration, immune-related functions and checkpoints were factors to affect prognoisis of pancreatic cancer. In summary, we identified the prognostic ferroptosis-related lncRNAs in pancreatic cancer and these lncRNAs may serve as therapeutic targets for pancreatic cancer.

scholarly journals Comparison of Breast Cancer Molecular Features and Survival by African and European Ancestry in The Cancer Genome Atlas

JAMA Oncology ◽  
2017 ◽  
Vol 3 (12) ◽  
pp. 1654 ◽  
Author(s):  
Dezheng Huo ◽  
Hai Hu ◽  
Suhn K. Rhie ◽  
Eric R. Gamazon ◽  
Andrew D. Cherniack ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
European Ancestry ◽  
Molecular Features ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Guoshu Bi ◽  
Yunyi Bian ◽  
Jiaqi Liang ◽  
Jiacheng Yin ◽  
Runmei Li ◽  
...  
Keyword(s):  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Score System ◽  
Molecular Features ◽  
Cancer Genome Atlas ◽  
Metabolic Heterogeneity ◽  
Tumor Types ◽  
Pan Cancer ◽  
Worse Prognosis

Abstract Background Generally, cancer cells undergo metabolic reprogramming to adapt to energetic and biosynthetic requirements that support their uncontrolled proliferation. However, the mutual relationship between two critical metabolic pathways, glycolysis and oxidative phosphorylation (OXPHOS), remains poorly defined. Methods We developed a “double-score” system to quantify glycolysis and OXPHOS in 9668 patients across 33 tumor types from The Cancer Genome Atlas and classified them into four metabolic subtypes. Multi-omics bioinformatical analyses was conducted to detect metabolism-related molecular features. Results Compared with patients with low glycolysis and high OXPHOS (LGHO), those with high glycolysis and low OXPHOS (HGLO) were consistently associated with worse prognosis. We identified common dysregulated molecular features between different metabolic subgroups across multiple cancers, including gene, miRNA, transcription factor, methylation, and somatic alteration, as well as investigated their mutual interfering relationships. Conclusion Overall, this work provides a comprehensive atlas of metabolic heterogeneity on a pan-cancer scale and identified several potential drivers of metabolic rewiring, suggesting corresponding prognostic and therapeutic utility.

scholarly journals Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuting He ◽  
Xiao Yu ◽  
Menggang Zhang ◽  
Wenzhi Guo
Keyword(s):  
Copy Number Variations ◽  
Regulatory Genes ◽  
The Cancer Genome Atlas ◽  
Cancer Pathogenesis ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Reversible Modification ◽  
Regulator Genes ◽  
Modified Nucleobases ◽  
Pan Cancer

Abstract Background 5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs. Methods Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers. Results After validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival. Conclusion Our results offered strong evidence and clinical implications for the involvement of m5C regulators.

scholarly journals Systematic analysis of aberrances of ferroptosis reveals its potential functional roles in cancer

2019 ◽  
Author(s):  
Zekun Liu ◽  
Qi Zhao ◽  
Zhi-Xiang Zuo ◽  
Shu-Qiang Yuan ◽  
Kai Yu ◽  
...  
Keyword(s):  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Aberrant Expression ◽  
Systematic Analysis ◽  
Functional Roles ◽  
Normal Tissues ◽  
Potential Index ◽  
Cancer Genome Atlas ◽  
Regulator Genes ◽  
Worse Prognosis

SummaryFerroptosis is a type of cell death that related to cancer, however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, copy number alterations (CNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers, and was associated with subtypes and clinical features. The FPI was negatively correlated with several metabolism pathways but positively associated with several important metastasis-related pathways and immune-related pathways. Higher FPI predicted worse prognosis in several tumors, while FPI and FRGs impacted drug sensitivity. Our study presents a systematical analysis of ferroptosis and its regulatory genes, and highlights the potential of ferroptosis-based cancer therapy.

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